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Zurli, Vanessa (2016) Novel strategies to improve anti-influenza vaccines. Positive contribution of adjuvanted immunization strategies during aging and in the resolution of viral-bacterial co-infections. [Tesi di dottorato]

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Abstract (inglese)

Despite the extensive use of anti-influenza vaccines during the last decades, influenza and its complications are still a major cause of morbidity and mortality worldwide. Older adults (>65 years) are particularly susceptible to influenza illness and it is estimated that approximately 90% of influenza deaths occurs in this population. Notably secondary bacterial infections (SBI), the majority of which are associated with S. pneumoniae or S. aureus, make a significant contribution to deaths during influenza epidemics and pandemics, through a phenomenon known as “excess mortality”. In order to reduce influenza-driven mortality, broader protective vaccines are needed and different strategies are possible. Among these, universal influenza vaccines or even broad-spectrum “pneumonia” vaccines targeting a range of different viral and bacterial respiratory pathogens are thinkable. To allow the design of such vaccines, a multitude of basic questions - such as the ideal vaccine composition, appropriate vaccine adjuvants and an understanding of the complex pathogen interactions - have to be addressed.
With the current work we wanted to address this specific medical need. In the first part we studied the special immunological pre-requisites for successful influenza vaccination in the elderly, while in the second part we extended our focus on the impact of different influenza vaccines on viral-bacterial co-infection.
Elderly people are particularly susceptible to influenza infection and its complications, but respond poorly to conventional vaccines. MF59-adjuvanted influenza vaccines have been specifically developed and licensed to target this age population and are considered - together with similar formulations - as the best strategy to prevent influenza disease in the context of immunosenescence. Yet, the development process was entirely empirical and it is only poorly understood how MF59 contributes to successfully restoring responsiveness to influenza vaccines in the elderly.
To deeply investigate the mechanism of action of MF59 in elderly subjects, we assessed immune response elicited by this adjuvant in old mice (>18 months). Our results showed that MF59 is able to potentiate responses against influenza antigens not only in young mice (6-8 weeks), but also in older ones: it enhanced immune cell recruitment at the site of injection, antigen-translocation to draining lymph nodes, CD4+ T cell response and germinal center formation. Yet, in line with clinical data, we noticed that hemagglutination inhibition (HI) antibody titers induced by MF59-adjuvanted vaccine in old mice were similar to those obtained in young ones immunized with not adjuvanted antigens arguing for the fact that MF59 can overcome some but not all aspects of immunosenescence. Accordingly, we wanted to dissect, which of the MF59-induced signaling cascades were impacted by aging. We recently showed in young mice, that transient ATP-release in injected muscle is an important contributor to adjuvanticity of MF59. Here we verified that also in aged mice ATP plays a central role for adjuvant activity. Yet, while in young mice it is not the only actor of adjuvanticity, in elderly other MF59-targeted immune pathways seem to be reduced due to “immunosenescence” or “inflammaging”.
MF59 is a safe, effective and well established vaccine adjuvant for influenza vaccine in humans with millions of doses administered. Whether there is room for further improvement of anti-influenza responses especially in the vulnerable elderly population has to be assessed.
Complications from secondary bacterial infection are a leading cause of influenza-associated morbidity and mortality. Anti-influenza vaccination is considered the best strategy to counteract primary viral disease spread. Moreover data from animal models suggest that it is also an effective method to prevent subsequent secondary bacterial pneumonia. Yet, currently approved influenza vaccines are typically assessed only for their capacity to elicit neutralizing antibodies specific for the homologous (vaccine-type) influenza strain. Protection against heterotypic (antigenic shift by mutations within influenza strain) or against heterologous (HA and/ or NA differing from those in the vaccine strain) influenza infection is studied to a lesser extent. And importantly, studies in humans have typically not been designed or appropriately powered to assess effectiveness against SBI.
It can be assumed that prevention of influenza infection through vaccination would also prevent complications such as SBI, but in case of heterotypic or heterologous virus challenge - as would easily occur during a normal influenza season - does partial protection significantly affect bacterial super-infections? Furthermore different types of influenza vaccines induce differential innate and adaptive responses in infected individuals that might impact positively or negatively on SBI. Does this occur and can it be measured?
We aimed to answer these questions in pre-clinical models of differently anti-influenza immunized mice. To that extent, we vaccinated BALB/c mice systemically with an A/California/7/2009 (H1N1) subunit vaccine either as plain antigens or adjuvanted with i) MF59 to induce a mixed Th1/Th2 response, ii) a combination of MF59 and CpG to get a more Th1-prone response or with iii) LTK63 administered via the mucosal route to obtain a Th1/Th17 polarized response. After vaccination mice were challenged with the heterologous mouse adapted strain A/Puerto Rico/8/1934 (H1N1) (PR8) and infection course and various aspects of immune response were dissected. We found that vaccination via different administration routes and adjuvants enhances immune responses to influenza virus infection by creating in the host a differently Th-polarized environment: all tested priming conditions induced strong vaccine-specific Th1, Th2 or Th17-polarized responses and anti-influenza antibody titers that quickly restored pre-infection immune environment in lung. On the contrary, plain immunization was significantly less effective: mice showed high viral titers similar to those of naïve ones and had overall higher influx of immune cells into the lung, an indication of ongoing inflammation. Notably mucosal vaccination with LTK63, though inducing lower HI titers, was equally good in protecting mice from influenza infection as systemic vaccination with MF59±CpG, strongly arguing for an important contribution of additional immune responses to protection in the setting of heterologous infection.
Secondly we asked if different flavors of immune responses during influenza infection would have a beneficial or detrimental impact on SBI caused by Methicillin-resistant S. aureus (MRSA) USA300, which has been recently associated with increasing cases of fulminant post-influenza pneumonia in humans. To this end we set up a new influenza-bacterial co-infection model in previously anti-influenza vaccinated mice. Immunizations were performed as before to skew the immune response towards different Th profiles. Mice were then infected with influenza PR8 virus and six days later co-infected with S. aureus. In this co-infection model we followed disease evolution by measuring mouse weight loss and pathogen clearance in lungs.
In this setting the differences between the single vaccination strategies became even more evident. While non-adjuvanted vaccine protected significantly from single influenza infection, it conferred little protection from viral-bacterial co-infection. Plain vaccinated mice were subjected to severe bacterial overgrowth and to high morbidity and mortality during SBI similarly to naïve mice. They just differed from naïve mice by their capability to control virus loads during SBI, while naïve mice showed a second wave of lung viral titer increase after bacterial infection that is a typical consequence of SBI. In contrast, we demonstrated that all adjuvanted vaccines were superior in preventing not only viral infection but also bacterial superinfection as compared to plain antigens vaccination. In particular Th1-prone mice efficiently controlled influenza infection better than those receiving other formulations and were nearly not affected by SBI.
Altogether our results showed that adjuvanted-influenza vaccines are an efficient method to counteract not only heterologous influenza infection, but also eventual SBI. Moreover we demonstrated that the adjuvant MF59 is extremely important to enhance immunity against virus antigens in aged preclinical models. MF59 could eventually be improved by adding immunopotentiators like CpG to further enhance Th1-prone immune responses. These responses seem to be superior for preventing both viral and viral-bacterial infection.

Abstract (italiano)

Nonostante che negli scorsi decenni si sia fatto un ampio uso dei vaccini anti-influenzali, l’influenza e le relative complicazioni sono tuttora tra le maggiori cause mondiali di morbilità e mortalità. Le persone più anziane (>65 anni di età) sono particolarmente sensibili all’influenza e si stima che all’interno di tale popolazione si ritrovi circa il 90% delle morti dovute alla malattia. Le infezioni batteriche secondarie (SBI) causate principalmente da S. pneumoniae e S. aureus rappresentano un’importante causa di morte durante le epidemie e pandemie influenzali attraverso un fenomeno conosciuto come “mortalità eccessiva”. Affinché si riesca a ridurre la mortalità dovuta all’influenza, occorrono vaccini con un più ampio spettro di protezione. Tra le possibili strategie troviamo vaccini influenzali universali o addirittura vaccini “generici” contro la polmonite in grado di difendere l’organismo da un’ampia gamma di virus e batteri patogeni per l’apparato respiratorio. Affinché si arrivi allo sviluppo di tali vaccini innovativi, occorre definire innanzitutto alcuni aspetti basilari, quali ad esempio la loro composizione ideale e la scelta degli adiuvanti appropriati, il tutto insieme ad una maggiore conoscenza delle complesse interazioni tra i patogeni target.
Nel presente lavoro di tesi abbiamo voluto approfondire questo specifico aspetto medico. Nella prima parte dello studio abbiamo definito quali sono i particolari prerequisiti immunologici per la buona riuscita della vaccinazione anti-influenzale negli anziani. Nella seconda parte invece ci siamo focalizzati sull’impatto che differenti tipologie di vaccini anti-influenzali possono avere sulla co-infezione tra il virus e un batterio.
La popolazione anziana, che è particolarmente suscettibile all’influenza e alle sue complicazioni, risponde scarsamente ai vaccini convenzionali. I vaccini adiuvantati con MF59 sono stati sviluppati e approvati specificatamente per questa popolazione target e, insieme a formulazioni simili, sono considerati ad oggi la migliore strategia per prevenire l’influenza nell’ambito dell’immunosenescenza. Tuttavia lo sviluppo di tali vaccini è stato puramente empirico e ben poco si sa di come MF59 contribuisca a ristabilire nelle persone anziane un’efficiente risposta al vaccino.
In questo studio abbiamo analizzato la risposta immunitaria indotta da MF59 in topi anziani (>18 mesi) in modo da definire meglio il meccanismo di azione dell’adiuvante nei soggetti in età avanzata. Dai nostri risultati si evince che MF59 è in grado di potenziare la risposta immunitaria nei confronti dell’influenza non solo nei topi giovani (6-8 settimane), ma anche in quelli più vecchi. Abbiamo dimostrato infatti che l’adiuvante induce robusto reclutamento di cellule immunitarie al sito d’iniezione del vaccino, potenzia la traslocazione dell’antigene ai linfonodi drenanti e incrementa la risposta delle cellule T CD4+ e la formazione dei centri germinativi. Tuttavia, in linea con i risultati clinici, i titoli anticorpali d’inibizione dell’emoagglutinazione (HI) indotti dalla vaccinazione con MF59 nei topi anziani raggiungono livelli simili a quelli ottenuti nei topi più giovani vaccinati senza l’adiuvante. Da questo risultato possiamo dedurre che MF59 è in grado di porre rimedio ad alcuni degli aspetti caratterizzanti l’immunosenescenza, ma non a tutti. In accordo con ciò, abbiamo voluto definire meglio quali tra le cascate di segnalazione indotte da MF59 è impattata dall’invecchiamento. In nostro gruppo ha recentemente dimostrato in topi giovani che l’iniezione di MF59 nel muscolo induce un rilascio transiente di ATP che si rivela poi importante per l’effetto adiuvante del prodotto. In questo lavoro di tesi abbiamo verificato che anche nei topi anziani il rilascio di ATP gioca un ruolo centrale per l’attività dell’adiuvante. Tuttavia, mentre nei topi più giovani tale rilascio non è l’unico “attore” del potenziamento immunologico indotto dall’adiuvante, in quelli più vecchi gli altri pathway avviati da MF59 sembrano essere impattati negativamente dall’immunosenescenza e dallo stato di continua infiammazione tipico degli anziani.
MF59 è un adiuvante sicuro ed efficace e il suo utilizzo nella vaccinazione anti-influenzale umana è ormai consolidato con milioni di dosi somministrate. Quello che resta da definire è se c’è la possibilità di un ulteriore miglioramento della risposta anti-influenzale soprattutto in una popolazione così vulnerabile come quella degli anziani.
Le cause principali di morbilità e mortalità associate con l’influenza sono da imputarsi alle SBI. La vaccinazione anti-influenzale è considerata ad oggi la migliore strategia per combattere la diffusione della malattia. Inoltre, dati risultanti da studi su modelli animali, rivelano che la vaccinazione anti-influenzale è anche un metodo efficace nella prevenzione di polmoniti batteriche conseguenti all’influenza. Purtroppo i vaccini attualmente in commercio sono testati soltanto per la loro capacità di indurre anticorpi neutralizzanti specifici per il virus influenzale omologo al ceppo contenuto nel vaccino stesso. Non sono molto diffusi studi riguardanti la protezione indotta dai vaccini nei casi d’infezioni di virus influenzali eterosubtipici (cioè varianti antigeniche dovute a mutazioni all’interno di un ceppo influenzale) o eterologhi (le cui proteine HA e/ o NA differiscono da quelle presenti nel vaccino). Inoltre occorre notare che non sono stati ancora stabiliti studi clinici appropriati per definire l’effettiva efficienza dei vaccini influenzali nei confronti delle SBI.
Si può facilmente assumere che la prevenzione dell’infezione influenzale indotta dalla vaccinazione possa anche prevenire le relative complicazioni come le SBI, ma in caso d’infezione di virus eterosubtipici o eterologhi - situazione che può normalmente verificarsi durante la stagione influenzale – quale impatto può avere una protezione parziale dall’influenza sulle superinfezioni batteriche? Inoltre formulazioni diverse dei vaccini anti-influenzali inducono negli individui infettati risposte immunitarie innate e adattative diverse che possono avere un impatto positivo o negativo sulle SBI. Questa situazione si verifica realmente e come può essere quantificata?
In questo lavoro ci siamo fissati l’obiettivo di rispondere a queste domande utilizzando come modello di studio pre-clinico topi immunizzati contro l’influenza mediante svariate formulazioni di vaccini. Brevemente i topi BALB/c sono stati vaccinati per via sistemica con il vaccino a subunità specifico per il virus A/California/7/2009 (H1N1) sia utilizzando gli antigeni influenzali da soli, sia in formulazioni adiuvantate con i) MF59 in modo da indurre una risposta mista Th1/Th2, ii) MF59+CpG per ottenere una risposta polarizzata verso il profilo Th1 o con iii) LTK63 somministrato per via mucosale affinché la risposta immunitaria fosse indirizzata verso un profilo Th1/Th17. Dopo la vaccinazione, i topi sono stati infettati col virus A/Puerto Rico/8/1934 (H1N1) (PR8): tale virus è eterologo rispetto agli antigeni contenuti nel vaccino utilizzato ed è un ceppo virale adattato al topo. Nel corso dello studio abbiamo seguito l’evoluzione dell’infezione e vari aspetti della risposta immunitaria. I nostri risultati dimostrano che la somministrazione del vaccino mediante vie diverse e l’utilizzo di svariati adiuvanti potenziano la risposta immunitaria nei confronti dell’infezione influenzale creando nell’ospite un ambiente polarizzato verso i diversi profili Th: tutte le condizioni d’immunizzazione testate inducono elevate risposte immunitarie polarizzate verso i profili Th1, Th2 o Th17 e titoli anticorpali in grado di ristabilire velocemente la situazione immunitaria del polmone ad un livello pari a quello presente prima dell’infezione. Al contrario, il vaccino non adiuvantato si è dimostrato significativamente meno efficiente: i topi mostrano elevati titoli virali simili a quelli dei topi naïve ed hanno un robusto influsso di cellule immunitarie all’interno dei polmoni che identifica l’instaurazione di un processo infiammatorio. Occorre notare che la vaccinazione mucosale adiuvantata con LTK63, pur inducendo titoli HI più bassi, stabilisce un livello di protezione dall’infezione pari a quello della vaccinazione sistemica con MF59±CpG. Questo ci fa supporre che nel contesto di un’infezione eterologa, ai fini della protezione, sia molto importante il contributo di risposte immunitarie addizionali alla risposta anticorpale sistemica.
Partendo dai risultati ottenuti, ci siamo chiesti se le varie tipologie di risposta immunitaria indotte durante l’infezione d’influenza avessero un impatto positivo o negativo su SBI causate da S. aureus USA300 resistente alla meticillina (MRSA). Questo ceppo batterico è stato infatti recentemente associato con un numero crescente di casi di polmonite fulminante post-influenzale. A questo scopo abbiamo stabilito un nuovo modello d’infezione influenzale-batterica nei topi vaccinati per l’influenza. Le immunizzazioni sono state eseguite come in precedenza in modo da polarizzare le risposte immunitarie verso i vari profili Th. In seguito i topi sono stati infettati col virus influenzale PR8 e sei giorni dopo co-infettati con S. aureus. In questo modello di co-infezione abbiamo seguito l’evolversi della malattia misurando il peso corporeo dei topi e quantificando la replicazione dei patogeni nei polmoni.
Nel nostro modello di co-infezione le differenze tra le singole strategie di vaccinazione si sono marcate ancora di più. Sebbene il vaccino non adiuvantato proteggesse abbastanza bene dalla semplice infezione influenzale, è in grado di conferire soltanto una protezione parziale durante la co-infezione. Infatti, i topi vaccinati con tale formulazione sono soggetti a un’incontrollata crescita batterica e mostrano elevati livelli di morbilità e mortalità comparabili a quelli dei topi naïve. Si discostano dai topi naïve soltanto per la loro capacità di controllare la replicazione virale durante la SBI: mentre i topi naïve mostrano una seconda ondata d’incremento del titolo virale nei polmoni dopo l’infezione batterica - tipica conseguenza della SBI -, i topi che avevano ricevuto il vaccino non adiuvantato continuano il controllo del virus indipendentemente dalla SBI. Comparando i risultati del vaccino non adiuvantato con quelli ottenuti dalle tre formulazioni contenenti adiuvanti, abbiamo dimostrato che tutti i vaccini adiuvantati sono superiori non solo nella prevenzione dell’influenza, ma anche nel caso della superinfezione batterica. In particolare i topi il cui sistema immunitario aveva una polarizzazione verso il profilo Th1 sono in grado di controllare più efficientemente l’infezione influenzale rispetto ai topi che avevano ricevuto una delle altre due formulazioni adiuvantate e inoltre la SBI non ha quasi impatto negativo su di loro.
Nel complesso i nostri risultati dimostrano che i vaccini influenzali adiuvantati sono un metodo efficiente per combattere non solo un’infezione influenzale eterologa, ma anche un’eventuale SBI. Abbiamo inoltre dimostrato che l’adiuvante MF59 è di estrema importanza per potenziare la risposta immunitaria nei confronti degli antigeni virali nel modello pre-clinico di topi anziani. MF59 può essere eventualmente implementato mediante l’aggiunta di “potenziatori” del sistema immunitario come ad esempio il CpG, in modo da rafforzare le risposte polarizzate verso il profilo Th1. Queste risposte, infatti, risultano essere superiori per la prevenzione sia della semplice infezione virale sia della co-infezione.

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Tipo di EPrint:Tesi di dottorato
Relatore:Montecucco, Cesare
Correlatore:Seubert, Anja
Dottorato (corsi e scuole):Ciclo 28 > Scuole 28 > BIOSCIENZE E BIOTECNOLOGIE > BIOLOGIA CELLULARE
Data di deposito della tesi:14 Gennaio 2016
Anno di Pubblicazione:14 Gennaio 2016
Parole chiave (italiano / inglese):influenza / influenza, elderly / anziani, vaccine adjuvants / adiuvanti per vaccini, S. aureus / S. aureus, co-infection / co-infezione
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/13 Biologia applicata
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:9036
Depositato il:06 Ott 2016 15:27
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I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

1. WHO. Influenza (Seasonal). Fact sheet N°211. 2014; Available from: www.who.int/mediacentre/factsheets/fs211/en/. Vai! Cerca con Google

2. McCullers, J.A., The co-pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Microbiol, 2014. 12(4): p. 252-62. Cerca con Google

3. Del Giudice, G. and R. Rappuoli, Inactivated and adjuvanted influenza vaccines. Curr Top Microbiol Immunol, 2015. 386: p. 151-80. Cerca con Google

4. Vono, M., et al., The adjuvant MF59 induces ATP release from muscle that potentiates response to vaccination. Proc Natl Acad Sci U S A, 2013. 110(52): p. 21095-100. Cerca con Google

5. Huber, V.C., et al., Contribution of vaccine-induced immunity toward either the HA or the NA component of influenza viruses limits secondary bacterial complications. J Virol, 2010. 84(8): p. 4105-8. Cerca con Google

6. Baudner, B.C., et al., MF59 emulsion is an effective delivery system for a synthetic TLR4 agonist (E6020). Pharm Res, 2009. 26(6): p. 1477-85. Cerca con Google

7. Gallorini, S., et al., Sublingual immunization with a subunit influenza vaccine elicits comparable systemic immune response as intramuscular immunization, but also induces local IgA and TH17 responses. Vaccine, 2014. 32(20): p. 2382-8. Cerca con Google

8. Centers for Disease, C. and Prevention, Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza--Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep, 2007. 56(14): p. 325-9. Cerca con Google

9. Smith, A.M., et al., Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae. PLoS Pathog, 2013. 9(3): p. e1003238. Cerca con Google

10. Stohr, K., Influenza--WHO cares. Lancet Infect Dis, 2002. 2(9): p. 517. Cerca con Google

11. Tosh, P.K., R.M. Jacobson, and G.A. Poland, Influenza vaccines: from surveillance through production to protection. Mayo Clin Proc, 2010. 85(3): p. 257-73. Cerca con Google

12. Palese, P. and M.L. Shaw, Orthomyxoviridae: The viruses and their replication., in Fields Virology, 5th ed., Lippincott Williams & Wilkins; Wolters Kluwer Business, Editor. 2007. p. 1647–1689. Cerca con Google

13. Bottcher-Friebertshauser, E., et al., The hemagglutinin: a determinant of pathogenicity. Curr Top Microbiol Immunol, 2014. 385: p. 3-34. Cerca con Google

14. Chiu, C., et al., B cell responses to influenza infection and vaccination. Curr Top Microbiol Immunol, 2015. 386: p. 381-98. Cerca con Google

15. Eichelberger, M.C. and H. Wan, Influenza neuraminidase as a vaccine antigen. Curr Top Microbiol Immunol, 2015. 386: p. 275-99. Cerca con Google

16. Pinto, L.H., L.J. Holsinger, and R.A. Lamb, Influenza virus M2 protein has ion channel activity. Cell, 1992. 69(3): p. 517-28. Cerca con Google

17. Zheng, W. and Y.J. Tao, Structure and assembly of the influenza A virus ribonucleoprotein complex. FEBS Lett, 2013. 587(8): p. 1206-14. Cerca con Google

18. Tong, S., et al., A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci U S A, 2012. 109(11): p. 4269-74. Cerca con Google

19. WHO, A revision of the system of nomenclature for influenza viruses: a WHO memorandum. Bull World Health Organ, 1980. 58(4): p. 585-91. Cerca con Google

20. Clancy, S., Genetics of the influenza virus. Nature Education, 2008. 1(1): p. 83. Cerca con Google

21. Wikipedia. Influenza. Available from: https://en.wikipedia.org/wiki/Influenza. Vai! Cerca con Google

22. De Jong, J.C., et al., Influenza virus: a master of metamorphosis. J Infect, 2000. 40(3): p. 218-28. Cerca con Google

23. Thomas, P.G., et al., Cell-mediated protection in influenza infection. Emerg Infect Dis, 2006. 12(1): p. 48-54. Cerca con Google

24. Hensley, S.E., et al., Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science, 2009. 326(5953): p. 734-6. Cerca con Google

25. Boni, M.F., et al., Influenza drift and epidemic size: the race between generating and escaping immunity. Theor Popul Biol, 2004. 65(2): p. 179-91. Cerca con Google

26. Kreijtz, J.H., R.A. Fouchier, and G.F. Rimmelzwaan, Immune responses to influenza virus infection. Virus Res, 2011. 162(1-2): p. 19-30. Cerca con Google

27. van de Sandt, C.E., J.H. Kreijtz, and G.F. Rimmelzwaan, Evasion of influenza A viruses from innate and adaptive immune responses. Viruses, 2012. 4(9): p. 1438-76. Cerca con Google

28. Herfst, S., et al., Airborne transmission of influenza A/H5N1 virus between ferrets. Science, 2012. 336(6088): p. 1534-41. Cerca con Google

29. Turner, D., et al., Systematic review and economic decision modelling for the prevention and treatment of influenza A and B. Health Technol Assess, 2003. 7(35): p. iii-iv, xi-xiii, 1-170. Cerca con Google

30. Nicholson, K.G., J.M. Wood, and M. Zambon, Influenza. Lancet, 2003. 362(9397): p. 1733-45. Cerca con Google

31. Johnson, N.P. and J. Mueller, Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic. Bull Hist Med, 2002. 76(1): p. 105-15. Cerca con Google

32. Morens, D.M., J.K. Taubenberger, and A.S. Fauci, Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis, 2008. 198(7): p. 962-70. Cerca con Google

33. Kilbourne, E.D., Influenza pandemics of the 20th century. Emerg Infect Dis, 2006. 12(1): p. 9-14. Cerca con Google

34. Novel Swine-Origin Influenza, A.V.I.T., et al., Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med, 2009. 360(25): p. 2605-15. Cerca con Google

35. Dawood, F.S., et al., Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis, 2012. 12(9): p. 687-95. Cerca con Google

36. Durbin, J.E., et al., Type I IFN modulates innate and specific antiviral immunity. J Immunol, 2000. 164(8): p. 4220-8. Cerca con Google

37. Manicassamy, B., et al., Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus. Proc Natl Acad Sci U S A, 2010. 107(25): p. 11531-6. Cerca con Google

38. Perrone, L.A., et al., H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog, 2008. 4(8): p. e1000115. Cerca con Google

39. Medzhitov, R., Toll-like receptors and innate immunity. Nat Rev Immunol, 2001. 1(2): p. 135-45. Cerca con Google

40. Iwasaki, A. and P.S. Pillai, Innate immunity to influenza virus infection. Nat Rev Immunol, 2014. 14(5): p. 315-28. Cerca con Google

41. Sanders, C.J., P.C. Doherty, and P.G. Thomas, Respiratory epithelial cells in innate immunity to influenza virus infection. Cell Tissue Res, 2011. 343(1): p. 13-21. Cerca con Google

42. Hogner, K., et al., Macrophage-expressed IFN-beta contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog, 2013. 9(2): p. e1003188. Cerca con Google

43. Kallfass, C., et al., Visualizing the beta interferon response in mice during infection with influenza A viruses expressing or lacking nonstructural protein 1. J Virol, 2013. 87(12): p. 6925-30. Cerca con Google

44. Jewell, N.A., et al., Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo. J Virol, 2007. 81(18): p. 9790-800. Cerca con Google

45. Kim, H.M., et al., Alveolar macrophages are indispensable for controlling influenza viruses in lungs of pigs. J Virol, 2008. 82(9): p. 4265-74. Cerca con Google

46. Tumpey, T.M., et al., Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J Virol, 2005. 79(23): p. 14933-44. Cerca con Google

47. Landsman, L. and S. Jung, Lung macrophages serve as obligatory intermediate between blood monocytes and alveolar macrophages. J Immunol, 2007. 179(6): p. 3488-94. Cerca con Google

48. Jayasekera, J.P., et al., Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice. J Gen Virol, 2006. 87(Pt 11): p. 3361-71. Cerca con Google

49. Lin, K.L., et al., CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J Immunol, 2008. 180(4): p. 2562-72. Cerca con Google

50. Peper, R.L. and H. Van Campen, Tumor necrosis factor as a mediator of inflammation in influenza A viral pneumonia. Microb Pathog, 1995. 19(3): p. 175-83. Cerca con Google

51. Arnon, T.I., et al., Recognition of viral hemagglutinins by NKp44 but not by NKp30. Eur J Immunol, 2001. 31(9): p. 2680-9. Cerca con Google

52. Mandelboim, O., et al., Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature, 2001. 409(6823): p. 1055-60. Cerca con Google

53. Hashimoto, G., P.F. Wright, and D.T. Karzon, Antibody-dependent cell-mediated cytotoxicity against influenza virus-infected cells. J Infect Dis, 1983. 148(5): p. 785-94. Cerca con Google

54. Sun, P.D., Structure and function of natural-killer-cell receptors. Immunol Res, 2003. 27(2-3): p. 539-48. Cerca con Google

55. Hashimoto, Y., et al., Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J Immunol, 2007. 178(4): p. 2448-57. Cerca con Google

56. Cao, W., et al., Rapid differentiation of monocytes into type I IFN-producing myeloid dendritic cells as an antiviral strategy against influenza virus infection. J Immunol, 2012. 189(5): p. 2257-65. Cerca con Google

57. Unkel, B., et al., Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Invest, 2012. 122(10): p. 3652-64. Cerca con Google

58. Narasaraju, T., et al., Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol, 2011. 179(1): p. 199-210. Cerca con Google

59. Tate, M.D., et al., Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol, 2009. 183(11): p. 7441-50. Cerca con Google

60. GeurtsvanKessel, C.H. and B.N. Lambrecht, Division of labor between dendritic cell subsets of the lung. Mucosal Immunol, 2008. 1(6): p. 442-50. Cerca con Google

61. Hintzen, G., et al., Induction of tolerance to innocuous inhaled antigen relies on a CCR7-dependent dendritic cell-mediated antigen transport to the bronchial lymph node. J Immunol, 2006. 177(10): p. 7346-54. Cerca con Google

62. Bhardwaj, N., et al., Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells. J Clin Invest, 1994. 94(2): p. 797-807. Cerca con Google

63. Hamilton-Easton, A. and M. Eichelberger, Virus-specific antigen presentation by different subsets of cells from lung and mediastinal lymph node tissues of influenza virus-infected mice. J Virol, 1995. 69(10): p. 6359-66. Cerca con Google

64. Yewdell, J.W., E. Reits, and J. Neefjes, Making sense of mass destruction: quantitating MHC class I antigen presentation. Nat Rev Immunol, 2003. 3(12): p. 952-61. Cerca con Google

65. Braciale, T.J., J. Sun, and T.S. Kim, Regulating the adaptive immune response to respiratory virus infection. Nat Rev Immunol, 2012. 12(4): p. 295-305. Cerca con Google

66. Kim, T.S. and T.J. Braciale, Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PLoS One, 2009. 4(1): p. e4204. Cerca con Google

67. Pulendran, B. and M.S. Maddur, Innate immune sensing and response to influenza. Curr Top Microbiol Immunol, 2015. 386: p. 23-71. Cerca con Google

68. Chiu, C. and P.J. Openshaw, Antiviral B cell and T cell immunity in the lungs. Nat Immunol, 2015. 16(1): p. 18-26. Cerca con Google

69. Gerhard, W., The role of the antibody response in influenza virus infection. Curr Top Microbiol Immunol, 2001. 260: p. 171-90. Cerca con Google

70. de Jong, J.C., et al., Haemagglutination-inhibiting antibody to influenza virus. Dev Biol (Basel), 2003. 115: p. 63-73. Cerca con Google

71. Knossow, M. and J.J. Skehel, Variation and infectivity neutralization in influenza. Immunology, 2006. 119(1): p. 1-7. Cerca con Google

72. Wilson, I.A. and N.J. Cox, Structural basis of immune recognition of influenza virus hemagglutinin. Annu Rev Immunol, 1990. 8: p. 737-71. Cerca con Google

73. Lofano, G., et al., B Cells and Functional Antibody Responses to Combat Influenza. Front Immunol, 2015. 6: p. 336. Cerca con Google

74. Yu, X., et al., Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature, 2008. 455(7212): p. 532-6. Cerca con Google

75. Bosch, B.J., et al., Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets. J Virol, 2010. 84(19): p. 10366-74. Cerca con Google

76. Johansson, B.E., D.J. Bucher, and E.D. Kilbourne, Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. J Virol, 1989. 63(3): p. 1239-46. Cerca con Google

77. Johansson, B.E., B. Grajower, and E.D. Kilbourne, Infection-permissive immunization with influenza virus neuraminidase prevents weight loss in infected mice. Vaccine, 1993. 11(10): p. 1037-9. Cerca con Google

78. Kilbourne, E.D., et al., Protection of mice with recombinant influenza virus neuraminidase. J Infect Dis, 2004. 189(3): p. 459-61. Cerca con Google

79. Ebrahimi, S.M. and M. Tebianian, Influenza A viruses: why focusing on M2e-based universal vaccines. Virus Genes, 2011. 42(1): p. 1-8. Cerca con Google

80. Fiers, W., et al., M2e-based universal influenza A vaccine. Vaccine, 2009. 27(45): p. 6280-3. Cerca con Google

81. Schotsaert, M., et al., Universal M2 ectodomain-based influenza A vaccines: preclinical and clinical developments. Expert Rev Vaccines, 2009. 8(4): p. 499-508. Cerca con Google

82. Sukeno, N., et al., Anti-nucleoprotein antibody response in influenza A infection. Tohoku J Exp Med, 1979. 128(3): p. 241-9. Cerca con Google

83. Lamere, M.W., et al., Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance. J Virol, 2011. 85(10): p. 5027-35. Cerca con Google

84. Carragher, D.M., et al., A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol, 2008. 181(6): p. 4168-76. Cerca con Google

85. Bodewes, R., A.D. Osterhaus, and G.F. Rimmelzwaan, Targets for the induction of protective immunity against influenza a viruses. Viruses, 2010. 2(1): p. 166-88. Cerca con Google

86. Sambhara, S., et al., Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function. Cell Immunol, 2001. 211(2): p. 143-53. Cerca con Google

87. Stavnezer, J. and C.T. Amemiya, Evolution of isotype switching. Semin Immunol, 2004. 16(4): p. 257-75. Cerca con Google

88. Fernandez Gonzalez, S., J.P. Jayasekera, and M.C. Carroll, Complement and natural antibody are required in the long-term memory response to influenza virus. Vaccine, 2008. 26 Suppl 8: p. I86-93. Cerca con Google

89. Jayasekera, J.P., E.A. Moseman, and M.C. Carroll, Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity. J Virol, 2007. 81(7): p. 3487-94. Cerca con Google

90. Armstrong, S.J. and N.J. Dimmock, Neutralization of influenza virus by low concentrations of hemagglutinin-specific polymeric immunoglobulin A inhibits viral fusion activity, but activation of the ribonucleoprotein is also inhibited. J Virol, 1992. 66(6): p. 3823-32. Cerca con Google

91. Mazanec, M.B., C.L. Coudret, and D.R. Fletcher, Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies. J Virol, 1995. 69(2): p. 1339-43. Cerca con Google

92. Voeten, J.T., et al., Use of recombinant nucleoproteins in enzyme-linked immunosorbent assays for detection of virus-specific immunoglobulin A (IgA) and IgG antibodies in influenza virus A- or B-infected patients. J Clin Microbiol, 1998. 36(12): p. 3527-31. Cerca con Google

93. Rothbarth, P.H., et al., Influenza virus serology--a comparative study. J Virol Methods, 1999. 78(1-2): p. 163-9. Cerca con Google

94. Koutsonanos, D.G., et al., Serological memory and long-term protection to novel H1N1 influenza virus after skin vaccination. J Infect Dis, 2011. 204(4): p. 582-91. Cerca con Google

95. Onodera, T., et al., Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection. Proc Natl Acad Sci U S A, 2012. 109(7): p. 2485-90. Cerca con Google

96. Jones, P.D. and G.L. Ada, Persistence of influenza virus-specific antibody-secreting cells and B-cell memory after primary murine influenza virus infection. Cell Immunol, 1987. 109(1): p. 53-64. Cerca con Google

97. Mosmann, T.R., et al., Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol, 1986. 136(7): p. 2348-57. Cerca con Google

98. Lund, J.M., et al., Coordination of early protective immunity to viral infection by regulatory T cells. Science, 2008. 320(5880): p. 1220-4. Cerca con Google

99. Justewicz, D.M., P.C. Doherty, and R.G. Webster, The B-cell response in lymphoid tissue of mice immunized with various antigenic forms of the influenza virus hemagglutinin. J Virol, 1995. 69(9): p. 5414-21. Cerca con Google

100. Scherle, P.A. and W. Gerhard, Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J Exp Med, 1986. 164(4): p. 1114-28. Cerca con Google

101. Belz, G.T., et al., Compromised influenza virus-specific CD8(+)-T-cell memory in CD4(+)-T-cell-deficient mice. J Virol, 2002. 76(23): p. 12388-93. Cerca con Google

102. Swain, S.L., K.K. McKinstry, and T.M. Strutt, Expanding roles for CD4(+) T cells in immunity to viruses. Nat Rev Immunol, 2012. 12(2): p. 136-48. Cerca con Google

103. Soghoian, D.Z. and H. Streeck, Cytolytic CD4(+) T cells in viral immunity. Expert Rev Vaccines, 2010. 9(12): p. 1453-63. Cerca con Google

104. Brown, D.M., et al., CD4 T cell-mediated protection from lethal influenza: perforin and antibody-mediated mechanisms give a one-two punch. J Immunol, 2006. 177(5): p. 2888-98. Cerca con Google

105. Lee, L.Y., et al., Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J Clin Invest, 2008. 118(10): p. 3478-90. Cerca con Google

106. Wilkinson, T.M., et al., Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med, 2012. 18(2): p. 274-80. Cerca con Google

107. Lamb, J.R., et al., In vitro influenza virus-specific antibody production in man: antigen-specific and HLA-restricted induction of helper activity mediated by cloned human T lymphocytes. J Immunol, 1982. 129(4): p. 1465-70. Cerca con Google

108. Okoye, I.S. and M.S. Wilson, CD4+ T helper 2 cells--microbial triggers, differentiation requirements and effector functions. Immunology, 2011. 134(4): p. 368-77. Cerca con Google

109. Maloy, K.J., et al., CD4(+) T cell subsets during virus infection. Protective capacity depends on effector cytokine secretion and on migratory capability. J Exp Med, 2000. 191(12): p. 2159-70. Cerca con Google

110. Coutelier, J.P., et al., IgG2a restriction of murine antibodies elicited by viral infections. J Exp Med, 1987. 165(1): p. 64-9. Cerca con Google

111. Graham, M.B., V.L. Braciale, and T.J. Braciale, Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection. J Exp Med, 1994. 180(4): p. 1273-82. Cerca con Google

112. Moran, T.M., et al., Interleukin-4 causes delayed virus clearance in influenza virus-infected mice. J Virol, 1996. 70(8): p. 5230-5. Cerca con Google

113. McKinstry, K.K., et al., IL-10 deficiency unleashes an influenza-specific Th17 response and enhances survival against high-dose challenge. J Immunol, 2009. 182(12): p. 7353-63. Cerca con Google

114. Crowe, C.R., et al., Critical role of IL-17RA in immunopathology of influenza infection. J Immunol, 2009. 183(8): p. 5301-10. Cerca con Google

115. Ye, P., et al., Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med, 2001. 194(4): p. 519-27. Cerca con Google

116. Nutt, S.L. and D.M. Tarlinton, Germinal center B and follicular helper T cells: siblings, cousins or just good friends? Nat Immunol, 2011. 12(6): p. 472-7. Cerca con Google

117. Boyden, A.W., K.L. Legge, and T.J. Waldschmidt, Pulmonary infection with influenza A virus induces site-specific germinal center and T follicular helper cell responses. PLoS One, 2012. 7(7): p. e40733. Cerca con Google

118. Lee, S.K., et al., B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells. J Exp Med, 2011. 208(7): p. 1377-88. Cerca con Google

119. Lu, K.T., et al., Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity, 2011. 35(4): p. 622-32. Cerca con Google

120. Nakanishi, Y., et al., CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature, 2009. 462(7272): p. 510-3. Cerca con Google

121. Assarsson, E., et al., Immunomic analysis of the repertoire of T-cell specificities for influenza A virus in humans. J Virol, 2008. 82(24): p. 12241-51. Cerca con Google

122. Kreijtz, J.H., et al., Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol, 2008. 82(11): p. 5161-6. Cerca con Google

123. Moffat, J.M., et al., Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection. Eur J Immunol, 2009. 39(5): p. 1203-10. Cerca con Google

124. Topham, D.J., R.A. Tripp, and P.C. Doherty, CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J Immunol, 1997. 159(11): p. 5197-200. Cerca con Google

125. Andrade, F., Non-cytotoxic antiviral activities of granzymes in the context of the immune antiviral state. Immunol Rev, 2010. 235(1): p. 128-46. Cerca con Google

126. van Domselaar, R. and N. Bovenschen, Cell death-independent functions of granzymes: hit viruses where it hurts. Rev Med Virol, 2011. 21(5): p. 301-14. Cerca con Google

127. UN Population Division. World Population Ageing: 1950-2050. 2002; Available from: http://www.un.org/esa/population/publications/worldageing19502050/. Vai! Cerca con Google

128. Ginaldi, L., et al., Immunosenescence and infectious diseases. Microbes Infect, 2001. 3(10): p. 851-7. Cerca con Google

129. Lelic, A., et al., The polyfunctionality of human memory CD8+ T cells elicited by acute and chronic virus infections is not influenced by age. PLoS Pathog, 2012. 8(12): p. e1003076. Cerca con Google

130. Olivieri, F., et al., Toll like receptor signaling in "inflammaging": microRNA as new players. Immun Ageing, 2013. 10(1): p. 11. Cerca con Google

131. Dewan, S.K., et al., Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Chin Med J (Engl), 2012. 125(18): p. 3325-31. Cerca con Google

132. Jenny, N.S., Inflammation in aging: cause, effect, or both? Discov Med, 2012. 13(73): p. 451-60. Cerca con Google

133. Frasca, D. and B.B. Blomberg, Aging affects human B cell responses. J Clin Immunol, 2011. 31(3): p. 430-5. Cerca con Google

134. Arnold, C.R., et al., Gain and loss of T cell subsets in old age--age-related reshaping of the T cell repertoire. J Clin Immunol, 2011. 31(2): p. 137-46. Cerca con Google

135. Su, D.M., D. Aw, and D.B. Palmer, Immunosenescence: a product of the environment? Curr Opin Immunol, 2013. 25(4): p. 498-503. Cerca con Google

136. Tezil, T. and H. Basaga, Modulation of cell death in age-related diseases. Curr Pharm Des, 2014. 20(18): p. 3052-67. Cerca con Google

137. Wang, C.H., et al., Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging. Exp Biol Med (Maywood), 2013. 238(5): p. 450-60. Cerca con Google

138. Lesourd, B., Nutritional factors and immunological ageing. Proc Nutr Soc, 2006. 65(3): p. 319-25. Cerca con Google

139. Kelley, K.W., D.A. Weigent, and R. Kooijman, Protein hormones and immunity. Brain Behav Immun, 2007. 21(4): p. 384-92. Cerca con Google

140. Fulop, T., et al., Aging, frailty and age-related diseases. Biogerontology, 2010. 11(5): p. 547-63. Cerca con Google

141. Moreno, G. and C.M. Mangione, Management of cardiovascular disease risk factors in older adults with type 2 diabetes mellitus: 2002-2012 literature review. J Am Geriatr Soc, 2013. 61(11): p. 2027-37. Cerca con Google

142. Franceschi, C., et al., Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev, 2007. 128(1): p. 92-105. Cerca con Google

143. Centers for Disease, C. and Prevention, Estimated influenza illnesses and hospitalizations averted by influenza vaccination - United States, 2012-13 influenza season. MMWR Morb Mortal Wkly Rep, 2013. 62(49): p. 997-1000. Cerca con Google

144. Haq, K. and J.E. McElhaney, Ageing and respiratory infections: the airway of ageing. Immunol Lett, 2014. 162(1 Pt B): p. 323-8. Cerca con Google

145. Monto, A.S., et al., Influenza control in the 21st century: Optimizing protection of older adults. Vaccine, 2009. 27(37): p. 5043-53. Cerca con Google

146. Hak, E., et al., Development and validation of a clinical prediction rule for hospitalization due to pneumonia or influenza or death during influenza epidemics among community-dwelling elderly persons. J Infect Dis, 2004. 189(3): p. 450-8. Cerca con Google

147. Metersky, M.L., et al., Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int J Infect Dis, 2012. 16(5): p. e321-31. Cerca con Google

148. Yoshikawa, T.T., Epidemiology and unique aspects of aging and infectious diseases. Clin Infect Dis, 2000. 30(6): p. 931-3. Cerca con Google

149. Thompson, W.W., et al., Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA, 2003. 289(2): p. 179-86. Cerca con Google

150. Molinari, N.A., et al., The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine, 2007. 25(27): p. 5086-96. Cerca con Google

151. Rapid Reference to Influenza Resource Center Team. Pathogenesis, Clinical Features and Diagnosis. Available from: http://www.rapidreferenceinfluenza.com/chapter/B978-0-7234-3433-7.50012-8/aim/introduction. Vai! Cerca con Google

152. Barker, W.H., H. Borisute, and C. Cox, A study of the impact of influenza on the functional status of frail older people. Arch Intern Med, 1998. 158(6): p. 645-50. Cerca con Google

153. Madjid, M., et al., Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34,892 subjects. Eur Heart J, 2007. 28(10): p. 1205-10. Cerca con Google

154. Nichol, K.L., et al., Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med, 2003. 348(14): p. 1322-32. Cerca con Google

155. Reichert, T.A., et al., Influenza and the winter increase in mortality in the United States, 1959-1999. Am J Epidemiol, 2004. 160(5): p. 492-502. Cerca con Google

156. Fleming, D.M., K.W. Cross, and R.S. Pannell, Influenza and its relationship to circulatory disorders. Epidemiol Infect, 2005. 133(2): p. 255-62. Cerca con Google

157. Rozzini, R. and M. Trabucchi, Pneumonia and mortality beyond hospital discharge in elderly patients. Chest, 2011. 139(2): p. 473-4; author reply 474-5. Cerca con Google

158. Mouton, C.P., et al., Common infections in older adults. Am Fam Physician, 2001. 63(2): p. 257-68. Cerca con Google

159. Panda, A., et al., Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol, 2010. 184(5): p. 2518-27. Cerca con Google

160. Stout-Delgado, H.W., et al., Impaired NLRP3 inflammasome function in elderly mice during influenza infection is rescued by treatment with nigericin. J Immunol, 2012. 188(6): p. 2815-24. Cerca con Google

161. Plowden, J., et al., Innate immunity in aging: impact on macrophage function. Aging Cell, 2004. 3(4): p. 161-7. Cerca con Google

162. Butcher, S.K., et al., Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol, 2001. 70(6): p. 881-6. Cerca con Google

163. Goronzy, J.J. and C.M. Weyand, Understanding immunosenescence to improve responses to vaccines. Nat Immunol, 2013. 14(5): p. 428-36. Cerca con Google

164. Nikolich-Zugich, J. and B.D. Rudd, Immune memory and aging: an infinite or finite resource? Curr Opin Immunol, 2010. 22(4): p. 535-40. Cerca con Google

165. Kogut, I., et al., B cell maintenance and function in aging. Semin Immunol, 2012. 24(5): p. 342-9. Cerca con Google

166. Eaton, S.M., et al., Age-related defects in CD4 T cell cognate helper function lead to reductions in humoral responses. J Exp Med, 2004. 200(12): p. 1613-22. Cerca con Google

167. Haynes, L. and A.C. Maue, Effects of aging on T cell function. Curr Opin Immunol, 2009. 21(4): p. 414-7. Cerca con Google

168. Wagar, L.E., et al., Influenza-specific T cells from older people are enriched in the late effector subset and their presence inversely correlates with vaccine response. PLoS One, 2011. 6(8): p. e23698. Cerca con Google

169. McElhaney, J.E., Influenza vaccine responses in older adults. Ageing Res Rev, 2011. 10(3): p. 379-88. Cerca con Google

170. Castle, S., et al., Evidence of enhanced type 2 immune response and impaired upregulation of a type 1 response in frail elderly nursing home residents. Mech Ageing Dev, 1997. 94(1-3): p. 7-16. Cerca con Google

171. McElhaney, J.E., The unmet need in the elderly: designing new influenza vaccines for older adults. Vaccine, 2005. 23 Suppl 1: p. S10-25. Cerca con Google

172. Lee, J.S., et al., Age-associated alteration in naive and memory Th17 cell response in humans. Clin Immunol, 2011. 140(1): p. 84-91. Cerca con Google

173. Po, J.L., et al., Age-associated decrease in virus-specific CD8+ T lymphocytes during primary influenza infection. Mech Ageing Dev, 2002. 123(8): p. 1167-81. Cerca con Google

174. Jiang, J., et al., Limited expansion of virus-specific CD8 T cells in the aged environment. Mech Ageing Dev, 2009. 130(11-12): p. 713-21. Cerca con Google

175. Gibson, K.L., et al., B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell, 2009. 8(1): p. 18-25. Cerca con Google

176. Boraschi, D. and P. Italiani, Immunosenescence and vaccine failure in the elderly: strategies for improving response. Immunol Lett, 2014. 162(1 Pt B): p. 346-53. Cerca con Google

177. Collins, S.D., The Influenza Epidemic of 1928-1929 with Comparative Data for 1918-1919. Am J Public Health Nations Health, 1930. 20(2): p. 119-29. Cerca con Google

178. van Asten, L., et al., Mortality attributable to 9 common infections: significant effect of influenza A, respiratory syncytial virus, influenza B, norovirus, and parainfluenza in elderly persons. J Infect Dis, 2012. 206(5): p. 628-39. Cerca con Google

179. Brundage, J.F., Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis, 2006. 6(5): p. 303-12. Cerca con Google

180. Finelli, L., et al., Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics, 2008. 122(4): p. 805-11. Cerca con Google

181. Trotter, Y., Jr., et al., Asian influenza in the United States, 1957-1958. Am J Hyg, 1959. 70(1): p. 34-50. Cerca con Google

182. Gillet, Y., et al., Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet, 2002. 359(9308): p. 753-9. Cerca con Google

183. Iverson, A.R., et al., Influenza virus primes mice for pneumonia from Staphylococcus aureus. J Infect Dis, 2011. 203(6): p. 880-8. Cerca con Google

184. McCullers, J.A., Do specific virus-bacteria pairings drive clinical outcomes of pneumonia? Clin Microbiol Infect, 2013. 19(2): p. 113-8. Cerca con Google

185. Watt, J.P., et al., Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet, 2009. 374(9693): p. 903-11. Cerca con Google

186. Charu, V., et al., Mortality burden of the A/H1N1 pandemic in Mexico: a comparison of deaths and years of life lost to seasonal influenza. Clin Infect Dis, 2011. 53(10): p. 985-93. Cerca con Google

187. Centers for Disease, C. and Prevention, Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - United States, May-August 2009. MMWR Morb Mortal Wkly Rep, 2009. 58(38): p. 1071-4. Cerca con Google

188. Mauad, T., et al., Lung pathology in fatal novel human influenza A (H1N1) infection. Am J Respir Crit Care Med, 2010. 181(1): p. 72-9. Cerca con Google

189. Rice, T.W., et al., Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med, 2012. 40(5): p. 1487-98. Cerca con Google

190. Nguyen, T., et al., Coinfection with Staphylococcus aureus increases risk of severe coagulopathy in critically ill children with influenza A (H1N1) virus infection. Crit Care Med, 2012. 40(12): p. 3246-50. Cerca con Google

191. McCullers, J.A. and V.C. Huber, Correlates of vaccine protection from influenza and its complications. Hum Vaccin Immunother, 2012. 8(1): p. 34-44. Cerca con Google

192. Smith, A.M. and J.A. McCullers, Secondary bacterial infections in influenza virus infection pathogenesis. Curr Top Microbiol Immunol, 2014. 385: p. 327-56. Cerca con Google

193. Metzger, D.W. and K. Sun, Immune dysfunction and bacterial coinfections following influenza. J Immunol, 2013. 191(5): p. 2047-52. Cerca con Google

194. Rynda-Apple, A., K.M. Robinson, and J.F. Alcorn, Influenza and Bacterial Superinfection: Illuminating the Immunologic Mechanisms of Disease. Infect Immun, 2015. 83(10): p. 3764-70. Cerca con Google

195. Loosli, C.G., et al., The destruction of type 2 pneumocytes by airborne influenza PR8-A virus; its effect on surfactant and lecithin content of the pneumonic lesions of mice. Chest, 1975. 67(2 Suppl): p. 7S-14S. Cerca con Google

196. Pittet, L.A., et al., Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae. Am J Respir Cell Mol Biol, 2010. 42(4): p. 450-60. Cerca con Google

197. McAuley, J.L., et al., PB1-F2 proteins from H5N1 and 20 century pandemic influenza viruses cause immunopathology. PLoS Pathog, 2010. 6(7): p. e1001014. Cerca con Google

198. Nugent, K.M. and E.L. Pesanti, Tracheal function during influenza infections. Infect Immun, 1983. 42(3): p. 1102-8. Cerca con Google

199. Alymova, I.V., et al., The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae. Antimicrob Agents Chemother, 2005. 49(1): p. 398-405. Cerca con Google

200. Plotkowski, M.C., et al., Adherence of type I Streptococcus pneumoniae to tracheal epithelium of mice infected with influenza A/PR8 virus. Am Rev Respir Dis, 1986. 134(5): p. 1040-4. Cerca con Google

201. Dockrell, D.H., M.K. Whyte, and T.J. Mitchell, Pneumococcal pneumonia: mechanisms of infection and resolution. Chest, 2012. 142(2): p. 482-91. Cerca con Google

202. Heilmann, C., Adhesion mechanisms of staphylococci. Adv Exp Med Biol, 2011. 715: p. 105-23. Cerca con Google

203. McCullers, J.A. and J.E. Rehg, Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor. J Infect Dis, 2002. 186(3): p. 341-50. Cerca con Google

204. Guarner, J. and R. Falcon-Escobedo, Comparison of the pathology caused by H1N1, H5N1, and H3N2 influenza viruses. Arch Med Res, 2009. 40(8): p. 655-61. Cerca con Google

205. McCullers, J.A. and K.C. Bartmess, Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis, 2003. 187(6): p. 1000-9. Cerca con Google

206. Camara, M., et al., Streptococcus pneumoniae produces at least two distinct enzymes with neuraminidase activity: cloning and expression of a second neuraminidase gene in Escherichia coli. Infect Immun, 1991. 59(8): p. 2856-8. Cerca con Google

207. Miller, M.L., et al., Hypersusceptibility to invasive pneumococcal infection in experimental sickle cell disease involves platelet-activating factor receptor. J Infect Dis, 2007. 195(4): p. 581-4. Cerca con Google

208. Martin, P. and S.J. Leibovich, Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol, 2005. 15(11): p. 599-607. Cerca con Google

209. Koppe, U., N. Suttorp, and B. Opitz, Recognition of Streptococcus pneumoniae by the innate immune system. Cell Microbiol, 2012. 14(4): p. 460-6. Cerca con Google

210. Loffler, B., et al., Pathogenesis of Staphylococcus aureus necrotizing pneumonia: the role of PVL and an influenza coinfection. Expert Rev Anti Infect Ther, 2013. 11(10): p. 1041-51. Cerca con Google

211. Hale, B.G., et al., The multifunctional NS1 protein of influenza A viruses. J Gen Virol, 2008. 89(Pt 10): p. 2359-76. Cerca con Google

212. Sun, K. and D.W. Metzger, Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection. Nat Med, 2008. 14(5): p. 558-64. Cerca con Google

213. Li, W., B. Moltedo, and T.M. Moran, Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of gammadelta T cells. J Virol, 2012. 86(22): p. 12304-12. Cerca con Google

214. Shahangian, A., et al., Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice. J Clin Invest, 2009. 119(7): p. 1910-20. Cerca con Google

215. Navarini, A.A., et al., Increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses. Proc Natl Acad Sci U S A, 2006. 103(42): p. 15535-9. Cerca con Google

216. Nakamura, S., K.M. Davis, and J.N. Weiser, Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice. J Clin Invest, 2011. 121(9): p. 3657-65. Cerca con Google

217. Kudva, A., et al., Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J Immunol, 2011. 186(3): p. 1666-74. Cerca con Google

218. Small, C.L., et al., Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung. J Immunol, 2010. 184(4): p. 2048-56. Cerca con Google

219. Ghoneim, H.E., P.G. Thomas, and J.A. McCullers, Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol, 2013. 191(3): p. 1250-9. Cerca con Google

220. Rynda-Apple, A., et al., Regulation of IFN-gamma by IL-13 dictates susceptibility to secondary postinfluenza MRSA pneumonia. Eur J Immunol, 2014. 44(11): p. 3263-72. Cerca con Google

221. Damjanovic, D., et al., Marked improvement of severe lung immunopathology by influenza-associated pneumococcal superinfection requires the control of both bacterial replication and host immune responses. Am J Pathol, 2013. 183(3): p. 868-80. Cerca con Google

222. Narayana Moorthy, A., et al., In vivo and in vitro studies on the roles of neutrophil extracellular traps during secondary pneumococcal pneumonia after primary pulmonary influenza infection. Front Immunol, 2013. 4: p. 56. Cerca con Google

223. Hussell, T. and M.M. Cavanagh, The innate immune rheostat: influence on lung inflammatory disease and secondary bacterial pneumonia. Biochem Soc Trans, 2009. 37(Pt 4): p. 811-3. Cerca con Google

224. van der Sluijs, K.F., et al., IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J Immunol, 2004. 172(12): p. 7603-9. Cerca con Google

225. Didierlaurent, A., et al., Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection. J Exp Med, 2008. 205(2): p. 323-9. Cerca con Google

226. Tuomanen, E.I., R. Austrian, and H.R. Masure, Pathogenesis of pneumococcal infection. N Engl J Med, 1995. 332(19): p. 1280-4. Cerca con Google

227. Weiss, S.J., Tissue destruction by neutrophils. N Engl J Med, 1989. 320(6): p. 365-76. Cerca con Google

228. Weeks-Gorospe, J.N., et al., Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with Gram-positive respiratory pathogens. J Virol, 2012. 86(17): p. 9035-43. Cerca con Google

229. Tashiro, M., et al., Role of Staphylococcus protease in the development of influenza pneumonia. Nature, 1987. 325(6104): p. 536-7. Cerca con Google

230. Wang, J., et al., Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages. Nat Commun, 2013. 4: p. 2106. Cerca con Google

231. Joyce, E.A., S.J. Popper, and S. Falkow, Streptococcus pneumoniae nasopharyngeal colonization induces type I interferons and interferon-induced gene expression. BMC Genomics, 2009. 10: p. 404. Cerca con Google

232. Ichinohe, T., et al., Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci U S A, 2011. 108(13): p. 5354-9. Cerca con Google

233. Abt, M.C., et al., Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity, 2012. 37(1): p. 158-70. Cerca con Google

234. Monto, A.S., The role of antivirals in the control of influenza. Vaccine, 2003. 21(16): p. 1796-800. Cerca con Google

235. Ling, L.M., et al., Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection. Clin Infect Dis, 2010. 50(7): p. 963-9. Cerca con Google

236. McCullers, J.A., Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza. J Infect Dis, 2004. 190(3): p. 519-26. Cerca con Google

237. White, M.R., et al., Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus. Am J Physiol Lung Cell Mol Physiol, 2005. 289(4): p. L606-16. Cerca con Google

238. Fedson, D.S., Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents: why they are needed and how they might work. Influenza Other Respir Viruses, 2009. 3(4): p. 129-42. Cerca con Google

239. Karlstrom, A., et al., Treatment with protein synthesis inhibitors improves outcomes of secondary bacterial pneumonia after influenza. J Infect Dis, 2009. 199(3): p. 311-9. Cerca con Google

240. Chaussee, M.S., et al., Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections. Vaccine, 2011. 29(21): p. 3773-81. Cerca con Google

241. Haynes, L., et al., Immunity to the conserved influenza nucleoprotein reduces susceptibility to secondary bacterial infections. J Immunol, 2012. 189(10): p. 4921-9. Cerca con Google

242. Sun, K., et al., Seasonal FluMist vaccination induces cross-reactive T cell immunity against H1N1 (2009) influenza and secondary bacterial infections. J Immunol, 2011. 186(2): p. 987-93. Cerca con Google

243. Couch, R.B., et al., Influenza: its control in persons and populations. J Infect Dis, 1986. 153(3): p. 431-40. Cerca con Google

244. Soema, P.C., et al., Current and next generation influenza vaccines: Formulation and production strategies. Eur J Pharm Biopharm, 2015. 94: p. 251-63. Cerca con Google

245. Wong, S.S. and R.J. Webby, Traditional and new influenza vaccines. Clin Microbiol Rev, 2013. 26(3): p. 476-92. Cerca con Google

246. Francis, T., Jr., Vaccination against influenza. Bull World Health Organ, 1953. 8(5-6): p. 725-41. Cerca con Google

247. Kitchen, L.W. and D.W. Vaughn, Role of U.S. military research programs in the development of U.S.-licensed vaccines for naturally occurring infectious diseases. Vaccine, 2007. 25(41): p. 7017-30. Cerca con Google

248. Parkman, P.D., et al., Summary of clinical trials of influenza virus vaccines in adults. J Infect Dis, 1977. 136 Suppl: p. S722-30. Cerca con Google

249. Gross, P.A. and F.A. Ennis, Influenza vaccine: split-product versus whole-virus types--How do they differ. N Engl J Med, 1977. 296(10): p. 567-8. Cerca con Google

250. Doroshenko, A. and S.A. Halperin, Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines). Expert Rev Vaccines, 2009. 8(6): p. 679-88. Cerca con Google

251. Chan, C.Y. and P.A. Tambyah, Preflucel(R): a Vero-cell culture-derived trivalent influenza vaccine. Expert Rev Vaccines, 2012. 11(7): p. 759-73. Cerca con Google

252. Le Ru, A., et al., Scalable production of influenza virus in HEK-293 cells for efficient vaccine manufacturing. Vaccine, 2010. 28(21): p. 3661-71. Cerca con Google

253. Petukhova, N.V., et al., Immunogenicity and protective efficacy of candidate universal influenza A nanovaccines produced in plants by Tobacco mosaic virus-based vectors. Curr Pharm Des, 2013. 19(31): p. 5587-600. Cerca con Google

254. Ledgerwood, J.E., et al., DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. Lancet Infect Dis, 2011. 11(12): p. 916-24. Cerca con Google

255. Smith, L.R., et al., Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine, 2010. 28(13): p. 2565-72. Cerca con Google

256. Petsch, B., et al., Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol, 2012. 30(12): p. 1210-6. Cerca con Google

257. Hekele, A., et al., Rapidly produced SAM((R)) vaccine against H7N9 influenza is immunogenic in mice. Emerg Microbes Infect, 2013. 2(8): p. e52. Cerca con Google

258. Ambrose, C.S. and M.J. Levin, The rationale for quadrivalent influenza vaccines. Hum Vaccin Immunother, 2012. 8(1): p. 81-8. Cerca con Google

259. Cox, R.J., Correlates of protection to influenza virus, where do we go from here? Hum Vaccin Immunother, 2013. 9(2): p. 405-8. Cerca con Google

260. Ohmit, S.E., et al., Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection. J Infect Dis, 2011. 204(12): p. 1879-85. Cerca con Google

261. al-Mazrou, A., et al., Comparison of adverse reactions to whole-virion and split-virion influenza vaccines in hospital personnel. CMAJ, 1991. 145(3): p. 213-8. Cerca con Google

262. Duxbury, A.E., A.W. Hampson, and J.G. Sievers, Antibody response in humans to deoxycholate-treated influenza virus vaccine. J Immunol, 1968. 101(1): p. 62-7. Cerca con Google

263. Laver, W.G. and R.G. Webster, Preparation and immunogenicity of an influenza virus hemagglutinin and neuraminidase subunit vaccine. Virology, 1976. 69(2): p. 511-22. Cerca con Google

264. Brady, M.I. and I.G. Furminger, A surface antigen influenza vaccine. 1. Purification of haemagglutinin and neuraminidase proteins. J Hyg (Lond), 1976. 77(2): p. 161-72. Cerca con Google

265. Squarcione, S., et al., Comparison of the reactogenicity and immunogenicity of a split and a subunit-adjuvanted influenza vaccine in elderly subjects. Vaccine, 2003. 21(11-12): p. 1268-74. Cerca con Google

266. Goodwin, K., C. Viboud, and L. Simonsen, Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine, 2006. 24(8): p. 1159-69. Cerca con Google

267. Gross, P.A., et al., A controlled double-blind comparison of reactogenicity, immunogenicity, and protective efficacy of whole-virus and split-product influenza vaccines in children. J Infect Dis, 1977. 136(5): p. 623-32. Cerca con Google

268. Fiore, A.E., et al., Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep, 2008. 57(RR-7): p. 1-60. Cerca con Google

269. Ansaldi, F., et al., Fluzone((R)) Intradermal vaccine: a promising new chance to increase the acceptability of influenza vaccination in adults. Expert Rev Vaccines, 2012. 11(1): p. 17-25. Cerca con Google

270. Baxter, R., et al., Evaluation of the safety, reactogenicity and immunogenicity of FluBlok(R) trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. Vaccine, 2011. 29(12): p. 2272-8. Cerca con Google

271. King, J.C., Jr., et al., Evaluation of the safety, reactogenicity and immunogenicity of FluBlok trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy children aged 6-59 months. Vaccine, 2009. 27(47): p. 6589-94. Cerca con Google

272. Herzog, C., et al., Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine. Vaccine, 2009. 27(33): p. 4381-7. Cerca con Google

273. Barria, M.I., et al., Localized mucosal response to intranasal live attenuated influenza vaccine in adults. J Infect Dis, 2013. 207(1): p. 115-24. Cerca con Google

274. Tosh, P.K., T.G. Boyce, and G.A. Poland, Flu myths: dispelling the myths associated with live attenuated influenza vaccine. Mayo Clin Proc, 2008. 83(1): p. 77-84. Cerca con Google

275. Carrat, F. and A. Flahault, Influenza vaccine: the challenge of antigenic drift. Vaccine, 2007. 25(39-40): p. 6852-62. Cerca con Google

276. McKee, A.S., M.W. Munks, and P. Marrack, How do adjuvants work? Important considerations for new generation adjuvants. Immunity, 2007. 27(5): p. 687-90. Cerca con Google

277. Tritto, E., F. Mosca, and E. De Gregorio, Mechanism of action of licensed vaccine adjuvants. Vaccine, 2009. 27(25-26): p. 3331-4. Cerca con Google

278. Coffman, R.L., A. Sher, and R.A. Seder, Vaccine adjuvants: putting innate immunity to work. Immunity, 2010. 33(4): p. 492-503. Cerca con Google

279. Even-Or, O., et al., Adjuvanted influenza vaccines. Expert Rev Vaccines, 2013. 12(9): p. 1095-108. Cerca con Google

280. Galli, G., et al., Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine. Proc Natl Acad Sci U S A, 2009. 106(19): p. 7962-7. Cerca con Google

281. Banzhoff, A., et al., MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS One, 2009. 4(2): p. e4384. Cerca con Google

282. Schwarz, T.F., et al., Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial induces strong and broad immune responsiveness to booster vaccination in adults. Vaccine, 2009. 27(45): p. 6284-90. Cerca con Google

283. Bresson, J.L., et al., Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet, 2006. 367(9523): p. 1657-64. Cerca con Google

284. Bernstein, D.I., et al., Effects of adjuvants on the safety and immunogenicity of an avian influenza H5N1 vaccine in adults. J Infect Dis, 2008. 197(5): p. 667-75. Cerca con Google

285. Manzoli, L., et al., Meta-analysis of the immunogenicity and tolerability of pandemic influenza A 2009 (H1N1) vaccines. PLoS One, 2011. 6(9): p. e24384. Cerca con Google

286. Tsai, T.F., Fluad(R)-MF59(R)-Adjuvanted Influenza Vaccine in Older Adults. Infect Chemother, 2013. 45(2): p. 159-74. Cerca con Google

287. Van Buynder, P.G., et al., The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine, 2013. 31(51): p. 6122-8. Cerca con Google

288. Zedda, L., et al., Dissecting the immune response to MF59-adjuvanted and nonadjuvanted seasonal influenza vaccines in children less than three years of age. Pediatr Infect Dis J, 2015. 34(1): p. 73-8. Cerca con Google

289. Della Cioppa, G., et al., Trivalent and quadrivalent MF59((R))-adjuvanted influenza vaccine in young children: a dose- and schedule-finding study. Vaccine, 2011. 29(47): p. 8696-704. Cerca con Google

290. Frey, S., et al., Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults. Vaccine, 2003. 21(27-30): p. 4234-7. Cerca con Google

291. O'Hagan, D.T., et al., The history of MF59((R)) adjuvant: a phoenix that arose from the ashes. Expert Rev Vaccines, 2013. 12(1): p. 13-30. Cerca con Google

292. Skowronski, D.M., et al., Effectiveness of AS03 adjuvanted pandemic H1N1 vaccine: case-control evaluation based on sentinel surveillance system in Canada, autumn 2009. BMJ, 2011. 342: p. c7297. Cerca con Google

293. Moris, P., et al., H5N1 influenza vaccine formulated with AS03 A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin Immunol, 2011. 31(3): p. 443-54. Cerca con Google

294. McElhaney, J.E., et al., AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial. Lancet Infect Dis, 2013. 13(6): p. 485-96. Cerca con Google

295. Durier, C., et al., Long-term immunogenicity of two doses of 2009 A/H1N1v vaccine with and without AS03(A) adjuvant in HIV-1-infected adults. AIDS, 2013. 27(1): p. 87-93. Cerca con Google

296. Fairhead, T., et al., Poor seroprotection but allosensitization after adjuvanted pandemic influenza H1N1 vaccine in kidney transplant recipients. Transpl Infect Dis, 2012. 14(6): p. 575-83. Cerca con Google

297. Calabro, S., et al., The adjuvant effect of MF59 is due to the oil-in-water emulsion formulation, none of the individual components induce a comparable adjuvant effect. Vaccine, 2013. 31(33): p. 3363-9. Cerca con Google

298. Ott, G., et al., MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol, 1995. 6: p. 277-96. Cerca con Google

299. Gasparini, R., et al., Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects. Eur J Epidemiol, 2001. 17(2): p. 135-40. Cerca con Google

300. Iob, A., et al., Evidence of increased clinical protection of an MF59-adjuvant influenza vaccine compared to a non-adjuvant vaccine among elderly residents of long-term care facilities in Italy. Epidemiol Infect, 2005. 133(4): p. 687-93. Cerca con Google

301. Puig-Barbera, J., et al., Effectiveness of MF59-adjuvanted subunit influenza vaccine in preventing hospitalisations for cardiovascular disease, cerebrovascular disease and pneumonia in the elderly. Vaccine, 2007. 25(42): p. 7313-21. Cerca con Google

302. Vesikari, T., et al., MF59-adjuvanted influenza vaccine (FLUAD) in children: safety and immunogenicity following a second year seasonal vaccination. Vaccine, 2009. 27(45): p. 6291-5. Cerca con Google

303. Fragapane, E., et al., A heterologous MF59-adjuvanted H5N1 prepandemic influenza booster vaccine induces a robust, cross-reactive immune response in adults and the elderly. Clin Vaccine Immunol, 2010. 17(11): p. 1817-9. Cerca con Google

304. Galli, G., et al., Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels. Proc Natl Acad Sci U S A, 2009. 106(10): p. 3877-82. Cerca con Google

305. Baldo, V., et al., Immunogenicity of three different influenza vaccines against homologous and heterologous strains in nursing home elderly residents. Clin Dev Immunol, 2010. 2010: p. 517198. Cerca con Google

306. Camilloni, B., et al., Cross-reactive antibodies in middle-aged and elderly volunteers after MF59-adjuvanted subunit trivalent influenza vaccine against B viruses of the B/Victoria or B/Yamagata lineages. Vaccine, 2009. 27(31): p. 4099-103. Cerca con Google

307. Ansaldi, F., et al., Cross-protection by MF59-adjuvanted influenza vaccine: neutralizing and haemagglutination-inhibiting antibody activity against A(H3N2) drifted influenza viruses. Vaccine, 2008. 26(12): p. 1525-9. Cerca con Google

308. Ott, G., G.L. Barchfeld, and G. Van Nest, Enhancement of humoral response against human influenza vaccine with the simple submicron oil/water emulsion adjuvant MF59. Vaccine, 1995. 13(16): p. 1557-62. Cerca con Google

309. De Donato, S., et al., Safety and immunogenicity of MF59-adjuvanted influenza vaccine in the elderly. Vaccine, 1999. 17(23-24): p. 3094-101. Cerca con Google

310. O'Hagan, D.T., et al., The mechanism of action of MF59 - an innately attractive adjuvant formulation. Vaccine, 2012. 30(29): p. 4341-8. Cerca con Google

311. Dupuis, M., D.M. McDonald, and G. Ott, Distribution of adjuvant MF59 and antigen gD2 after intramuscular injection in mice. Vaccine, 1999. 18(5-6): p. 434-9. Cerca con Google

312. Dupuis, M., et al., Dendritic cells internalize vaccine adjuvant after intramuscular injection. Cell Immunol, 1998. 186(1): p. 18-27. Cerca con Google

313. Dupuis, M., et al., Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis. Eur J Immunol, 2001. 31(10): p. 2910-8. Cerca con Google

314. Seubert, A., et al., The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol, 2008. 180(8): p. 5402-12. Cerca con Google

315. Mosca, F., et al., Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci U S A, 2008. 105(30): p. 10501-6. Cerca con Google

316. Calabro, S., et al., Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine, 2011. 29(9): p. 1812-23. Cerca con Google

317. Wack, A., et al., Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice. Vaccine, 2008. 26(4): p. 552-61. Cerca con Google

318. O'Hagan, D.T. and N.M. Valiante, Recent advances in the discovery and delivery of vaccine adjuvants. Nat Rev Drug Discov, 2003. 2(9): p. 727-35. Cerca con Google

319. Steinhagen, F., et al., TLR-based immune adjuvants. Vaccine, 2011. 29(17): p. 3341-55. Cerca con Google

320. Wong, G.H. and D.V. Goeddel, Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. Nature, 1986. 323(6091): p. 819-22. Cerca con Google

321. Huber, V.C., et al., Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza. Clin Vaccine Immunol, 2006. 13(9): p. 981-90. Cerca con Google

322. McElhaney, J.E., R.N. Coler, and S.L. Baldwin, Immunologic correlates of protection and potential role for adjuvants to improve influenza vaccines in older adults. Expert Rev Vaccines, 2013. 12(7): p. 759-66. Cerca con Google

323. Behzad, H., et al., GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults. J Infect Dis, 2012. 205(3): p. 466-73. Cerca con Google

324. Krieg, A.M., Immune effects and mechanisms of action of CpG motifs. Vaccine, 2000. 19(6): p. 618-22. Cerca con Google

325. Sugai, T., et al., A CpG-containing oligodeoxynucleotide as an efficient adjuvant counterbalancing the Th1/Th2 immune response in diphtheria-tetanus-pertussis vaccine. Vaccine, 2005. 23(46-47): p. 5450-6. Cerca con Google

326. Klinman, D.M., et al., Use of CpG oligodeoxynucleotides as immune adjuvants. Immunol Rev, 2004. 199: p. 201-16. Cerca con Google

327. Vajdy, M., et al., Hepatitis C virus polyprotein vaccine formulations capable of inducing broad antibody and cellular immune responses. J Gen Virol, 2006. 87(Pt 8): p. 2253-62. Cerca con Google

328. Lin, Y., et al., Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and nonstructural proteins 3, 4, and 5. J Virol, 2008. 82(15): p. 7492-503. Cerca con Google

329. Yang, M., et al., MF59 formulated with CpG ODN as a potent adjuvant of recombinant HSP65-MUC1 for inducing anti-MUC1+ tumor immunity in mice. Int Immunopharmacol, 2012. 13(4): p. 408-16. Cerca con Google

330. Holmgren, J. and C. Czerkinsky, Mucosal immunity and vaccines. Nat Med, 2005. 11(4 Suppl): p. S45-53. Cerca con Google

331. Fujihashi, K., et al., A dilemma for mucosal vaccination: efficacy versus toxicity using enterotoxin-based adjuvants. Vaccine, 2002. 20(19-20): p. 2431-8. Cerca con Google

332. Lewis, D.J., et al., Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PLoS One, 2009. 4(9): p. e6999. Cerca con Google

333. Cuburu, N., et al., Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine, 2007. 25(51): p. 8598-610. Cerca con Google

334. Song, J.H., et al., Sublingual vaccination with influenza virus protects mice against lethal viral infection. Proc Natl Acad Sci U S A, 2008. 105(5): p. 1644-9. Cerca con Google

335. Eichelberger, M., et al., FDA/NIH/WHO public workshop on immune correlates of protection against influenza A viruses in support of pandemic vaccine development, Bethesda, Maryland, US, December 10-11, 2007. Vaccine, 2008. 26(34): p. 4299-303. Cerca con Google

336. Cwach, K.T., et al., Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays. Influenza Other Respir Viruses, 2012. 6(2): p. 127-35. Cerca con Google

337. Berkhoff, E.G., et al., Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes. J Virol, 2005. 79(17): p. 11239-46. Cerca con Google

338. Rimmelzwaan, G.F., et al., Influenza virus CTL epitopes, remarkably conserved and remarkably variable. Vaccine, 2009. 27(45): p. 6363-5. Cerca con Google

339. Trzcinski, K., et al., Protection against nasopharyngeal colonization by Streptococcus pneumoniae is mediated by antigen-specific CD4+ T cells. Infect Immun, 2008. 76(6): p. 2678-84. Cerca con Google

340. Weinberger, B., et al., Biology of immune responses to vaccines in elderly persons. Clin Infect Dis, 2008. 46(7): p. 1078-84. Cerca con Google

341. Sambhara, S. and J.E. McElhaney, Immunosenescence and influenza vaccine efficacy. Curr Top Microbiol Immunol, 2009. 333: p. 413-29. Cerca con Google

342. De Gregorio, E., U. D'Oro, and A. Wack, Immunology of TLR-independent vaccine adjuvants. Curr Opin Immunol, 2009. 21(3): p. 339-45. Cerca con Google

343. Kool, M., K. Fierens, and B.N. Lambrecht, Alum adjuvant: some of the tricks of the oldest adjuvant. J Med Microbiol, 2012. 61(Pt 7): p. 927-34. Cerca con Google

344. Haq, K. and J.E. McElhaney, Immunosenescence: Influenza vaccination and the elderly. Curr Opin Immunol, 2014. 29: p. 38-42. Cerca con Google

345. Rumke, H.C., et al., Selection of an adjuvant for seasonal influenza vaccine in elderly people: modelling immunogenicity from a randomized trial. BMC Infect Dis, 2013. 13: p. 348. Cerca con Google

346. O'Hagan, D.T., et al., MF59 adjuvant: the best insurance against influenza strain diversity. Expert Rev Vaccines, 2011. 10(4): p. 447-62. Cerca con Google

347. Mastelic Gavillet, B., et al., MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life. J Immunol, 2015. 194(10): p. 4836-45. Cerca con Google

348. Spensieri, F., et al., Human circulating influenza-CD4+ ICOS1+IL-21+ T cells expand after vaccination, exert helper function, and predict antibody responses. Proc Natl Acad Sci U S A, 2013. 110(35): p. 14330-5. Cerca con Google

349. La Gruta, N.L. and S.J. Turner, T cell mediated immunity to influenza: mechanisms of viral control. Trends Immunol, 2014. 35(8): p. 396-402. Cerca con Google

350. Seubert, A., et al., Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88. Proc Natl Acad Sci U S A, 2011. 108(27): p. 11169-74. Cerca con Google

351. Caproni, E., et al., MF59 and Pam3CSK4 boost adaptive responses to influenza subunit vaccine through an IFN type I-independent mechanism of action. J Immunol, 2012. 188(7): p. 3088-98. Cerca con Google

352. Huber, V.C., P.G. Thomas, and J.A. McCullers, A multi-valent vaccine approach that elicits broad immunity within an influenza subtype. Vaccine, 2009. 27(8): p. 1192-200. Cerca con Google

353. Reed, L.J. and H. Muench, A simple method of estimating fifty percent endpoints. The American Journal of Hygiene, 1938. 27: p. 493–497. Cerca con Google

354. Della Cioppa, G., et al., Superior immunogenicity of seasonal influenza vaccines containing full dose of MF59 ((R)) adjuvant: results from a dose-finding clinical trial in older adults. Hum Vaccin Immunother, 2012. 8(2): p. 216-27. Cerca con Google

355. Della Cioppa, G., et al., A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59(R)-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration. Hum Vaccin Immunother, 2014. 10(6): p. 1701-10. Cerca con Google

356. Bender, B.S., et al., Pulmonary immune response of young and aged mice after influenza challenge. J Lab Clin Med, 1995. 126(2): p. 169-77. Cerca con Google

357. Toapanta, F.R. and T.M. Ross, Impaired immune responses in the lungs of aged mice following influenza infection. Respir Res, 2009. 10: p. 112. Cerca con Google

358. Lofano, G., et al., Oil-in-Water Emulsion MF59 Increases Germinal Center B Cell Differentiation and Persistence in Response to Vaccination. J Immunol, 2015. 195(4): p. 1617-27. Cerca con Google

359. Cantisani, R., et al., Vaccine adjuvant MF59 promotes retention of unprocessed antigen in lymph node macrophage compartments and follicular dendritic cells. J Immunol, 2015. 194(4): p. 1717-25. Cerca con Google

360. Heufler, C., F. Koch, and G. Schuler, Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med, 1988. 167(2): p. 700-5. Cerca con Google

361. Makino, M., et al., Impaired maturation and function of dendritic cells by mycobacteria through IL-1beta. Eur J Immunol, 2006. 36(6): p. 1443-52. Cerca con Google

362. Franceschi, C., Continuous remodeling as a key to aging and survival: an interview with Claudio Franceschi. Interview by Suresh I S Rattan. Biogerontology, 2003. 4(5): p. 329-34. Cerca con Google

363. Giunta, S., Is inflammaging an auto[innate]immunity subclinical syndrome? Immun Ageing, 2006. 3: p. 12. Cerca con Google

364. Brito, L.A. and D.T. O'Hagan, Designing and building the next generation of improved vaccine adjuvants. J Control Release, 2014. 190: p. 563-79. Cerca con Google

365. Glezen, W.P., Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev, 1982. 4: p. 25-44. Cerca con Google

366. McCullers, J.A., Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev, 2006. 19(3): p. 571-82. Cerca con Google

367. Fowlkes, A.L., et al., Epidemiology of 2009 pandemic influenza A (H1N1) deaths in the United States, April-July 2009. Clin Infect Dis, 2011. 52 Suppl 1: p. S60-8. Cerca con Google

368. Trinchieri, G., Type I interferon: friend or foe? J Exp Med, 2010. 207(10): p. 2053-63. Cerca con Google

369. Robinson, K.M., et al., Influenza A virus exacerbates Staphylococcus aureus pneumonia in mice by attenuating antimicrobial peptide production. J Infect Dis, 2014. 209(6): p. 865-75. Cerca con Google

370. Sun, K. and D.W. Metzger, Influenza infection suppresses NADPH oxidase-dependent phagocytic bacterial clearance and enhances susceptibility to secondary methicillin-resistant Staphylococcus aureus infection. J Immunol, 2014. 192(7): p. 3301-7. Cerca con Google

371. Kommareddy, S., et al., Preparation of highly concentrated influenza vaccine for use in novel delivery approaches. J Pharm Sci, 2013. 102(3): p. 866-75. Cerca con Google

372. Giuliani, M.M., et al., Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity. J Exp Med, 1998. 187(7): p. 1123-32. Cerca con Google

373. Brazzoli, M., et al., Induction of broad-based immunity and protective efficacy by self-amplifying mRNA vaccines encoding influenza virus hemagglutinin. Journal of Virology (Accepted), 2015. Cerca con Google

374. Chow, J., et al., Host-bacterial symbiosis in health and disease. Adv Immunol, 2010. 107: p. 243-74. Cerca con Google

375. Erturk-Hasdemir, D. and D.L. Kasper, Resident commensals shaping immunity. Curr Opin Immunol, 2013. 25(4): p. 450-5. Cerca con Google

376. Nunes, A., et al., Adaptive evolution of the Chlamydia trachomatis dominant antigen reveals distinct evolutionary scenarios for B- and T-cell epitopes: worldwide survey. PLoS One, 2010. 5(10). Cerca con Google

377. FDA. Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines. 2007; Available from: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm074794.htm. Vai! Cerca con Google

378. Settembre, E.C., P.R. Dormitzer, and R. Rappuoli, Bringing influenza vaccines into the 21st century. Hum Vaccin Immunother, 2014. 10(3): p. 600-4. Cerca con Google

379. Osterholm, M.T., et al., Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis, 2012. 12(1): p. 36-44. Cerca con Google

380. Jefferson, T., et al., Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev, 2012. 8: p. CD004879. Cerca con Google

381. Vesikari, T., et al., Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med, 2011. 365(15): p. 1406-16. Cerca con Google

382. Tu, W., et al., Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol, 2010. 84(13): p. 6527-35. Cerca con Google

383. Alam, S. and A.J. Sant, Infection with seasonal influenza virus elicits CD4 T cells specific for genetically conserved epitopes that can be rapidly mobilized for protective immunity to pandemic H1N1 influenza virus. J Virol, 2011. 85(24): p. 13310-21. Cerca con Google

384. Kreijtz, J.H., et al., Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine, 2007. 25(4): p. 612-20. Cerca con Google

385. Kreijtz, J.H., et al., Infection of m Cerca con Google

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