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Sicurella, Mariaconcetta (2012) Studi di immunogenicitĂ  ed efficacia di vettori HSV per lo sviluppo di un vaccino contro l'infezione da Herpes Simplex. [Tesi di dottorato]

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Abstract (inglese)

Introduction
Herpes simplex virus (HSV) is a relevant human pathogen widespread in the human population worldwide. The virus multiplies in the epithelial cells at the portal of entry, infects sensory nerve endings innervating the site of multiplication, where it establishes a latent infection. HSV-1 and HSV-2 genotypes can cause a variety of recurrent clinical illnesses including cold sores, keratitis, meningitis, encephalitis and genital infections that are characterized by pain, ulceration and increased risk of developing cervical cancer and acquiring other sexually transmitted infections, including HIV infection. In the last, 30 years several studies were devoted to the development of anti-HSV vaccines. Unfortunately, and in spite of numerous attempts with recombinant non-replicating viral vectors based on HSV, Adenovirus, vaccinia virus, recombinant HSV glycoproteins, attenuated live viruses, no anti-HSV vaccine is still available. Identification of adjuvants that can promote Th1 immune response induction, not only against dominant epitopes but also against subdominant epitopes, is a key point for the development of novel vaccine strategies against HSV infection.

Aim
In the present study, we describe the construction and the in vitro and in vivo characterization of a replication-defective or non-replicative HSV-1-based vectors deleted of multiple immediate early regulatory genes and containing a deletion in the non essential UL41 locus. We investigated the ability of a recombinant replication-defective or non replicative HSV-1 vectors encoding the HIV-1 Tat protein to induce long-term HSV-specific immune responses in a murine model. In this context, in the present study we have investigated whether the HIV-1 Tat protein may act as the molecule capable of inducing such broad and protective immunity against HSV. The ability of the vectors ( HSV1-Tat or HSV1-LacZ, HSVTB5gJTat or HSVTB5gJHE) to elicit protective immune responses in Balb/C and C57BL/6 mice upon challenge with wild-type HSV-1 or HSV-2 will be described.

Method
Generation of recombinant replication-defective or non replicative HSV-l vectors, Western blot analysis, virus stock purification, immunization protocols, splenocyte purification, Elispot assay, ELISA assay.



Results
The replication-defective or non-replicative HSV-1 vectors mantain the capacity to infect both dividing and non dividing cells of different species. They are safer compare to wild-type herpes virus because they are anable to replicate. The results indicate that Tat plays a major role in conferring protective immune-responses against HSV infection in both mice strains since only mice primed with the live attenuated (HSV1-Tat) or non replicative (HSVTB5gJTat) vectors, were protected from death after receiving a lethal dose of wild-type HSV-1 or HSV-2. The vectors administration by the intravaginally or intradermic route elicit specific immune responses in mice, mediating an increase of anti-HSV cellular immune responses characterized by the presence of high levels of IFN-Îł. Moreover the vectors mediate an increase of anti-HSV humorale immune responses, as compared to control (HSV1LVLacZ) vector, characterized by the presence of high levels IgG, subtype IgG2a. This work demonstrates that HSV recombinant vectors and HIV Tat protein, selected for this study, can be combined to increase and broad Th1-like and CTL responses against HSV epitopes. Our results indicate that the co-expression of Tat protein is important to induce a protective response in both mice strain even if the responses are different depending on the genetic background. In these mice stronger and broader immune responses against HSV subdominant epitopes are crucial for protection from death.

Conclusion
This study shows that the replicative or non replicative vectors expressing Tat are safe since no adverse effects were observed during the experimental protocols. These outcomes are very promising for the development of a novel generation of effective HSV vaccines.

Abstract (italiano)

Introduzione
Herpes simplex virus (HSV) è un patogeno molto diffuso nella popolazione mondiale umana. Il virus utilizza le cellule epiteliali come portale d'ingresso, in tali cellule replica e raggiunge le terminazioni nervose, nelle quali instaura la latenza. I due genotipi HSV-1 e HSV-2 possono causare diverse patologie cliniche, compresi l’ herpes labiale, cheratiti, meningiti, encefaliti e infezioni genitali, caratterizzate da dolore, ulcere e aumento del rischio di sviluppare il cancro del collo dell'utero e l'acquisizione di altre infezioni sessualmente trasmissibili, tra cui l'infezione da HIV. Negli ultimi 30 anni diversi studi sono stati dedicati allo sviluppo di vaccini anti-HSV. Purtroppo, e nonostante numerosi tentativi, un vaccino anti-HSV non è ancora disponibile. Per la realizzazione del vaccino sono stati proposti e sperimentati diversi sistemi: Adenovirus, vaccinia virus, virus ricombinanti esprimenti le glicoproteine di HSV, virus vivi attenuati, ma nessuno a portato ai risultati sperati. L’identificazione di adiuvanti in grado di promuovere dei segnali atti a favorire l'emergere di una risposta immunitaria Th1 non solo contro epitopi dominanti, ma anche contro epitopi subdominanti, che sono cruciali per bloccare la riattivazione virale è un punto chiave per lo sviluppo di nuove strategie di vaccino contro l'infezione da HSV.
Scopo
In questo studi l’obiettivo principale è stato quello di costruire e caratterizzare in vitro e in vivo dei vettori HSV a replicazione attenuata e non replicativi deleti di più geni regolatori precoci e/o contenenti una delezione del locus non essenziali UL41. Abbiamo studiato la capacità di vettori replicativi e non di codificare per la proteina Tat di HIV-1, per indurre risposte immunitarie HSV-specifiche a lungo termine in un modello murino. In questo contesto, abbiamo valutato se la proteina Tat di HIV-1 potesse agire come molecola in grado di generare un immunità ad ampio spettro contro l’infezione da HSV. Inoltre è stata valutata la capacità dei vettori (HSV1-Tat o HSV1-LacZ, HSVTB5gJTat o HSVTB5gJHE) di indurre una risposta immunitaria protettiva nei topi Balb/C e C57BL/6 in seguito ad un infezione con una dose letale di HSV-1 o HSV-2 wild-type.
Metodi
Costruzione e Caratterizzazione dei vettori replicativi attenuati e non replicativi, Colture cellulari, Analisi Western Blot, Purificazione di stock virali, Animali e protocolli di immunizzazione, Purificazione degli splenociti, Saggio Elispot, Saggio ELISA.
Risultati
I vettori HSV replicativi attenuati e non replicativi conservano la capacità di infettare cellule in divisione e non di diverse specie, comportandosi come virus wild-type, ma risultano più sicuri a causa della loro incapacità di replicare e esprimere proteine virali dopo l'infezione. I risultati indicano che la proteina Tat svolge un ruolo importante nel conferire protezione immunitaria contro l'infezione da HSV in entrambi i ceppi di topi in quanto solo i topi vaccinati con i vettori replicativi attenuati (HSV1-Tat) o non replicativi (HSVTB5gJTat) esprimenti Tat risultavano protetti dalla morte dopo aver ricevuto una dose letale di HSV-1 o HSV-2 wild-type. La somministrazione dei vettori per via intravaginale o intradermica genera specifiche risposte immunitarie nei topi, media un incremento della risposta cellulare anti-HSV caratterizzata dalla presenza di alti livelli di IFN-γ, un incremento della risposta umorale anti-HSV rispetto al vettore di controllo (HSV1LVLacZ) caratterizzato dalla presenza di elevati livelli di IgG, più precisamente del sottotipo IgG2a. Questo lavoro dimostra che i vettori HSV associati alla proteina ricombinante Tat di HIV possono essere combinati per aumentare e ampliare la risposta di tipo Th1 e CTL contro epitopi immunodominanti e subdominanti di HSV. I nostri risultati indicano che la co-espressione della proteina Tat è importante per indurre una risposta protettiva in entrambi i modelli murini scelti, anche se le risposte sono diverse a seconda del background genetico. In questi topi la risposta immunitaria contro epitopi subdominanti di HSV è risultata essere fondamentale per una indurre una maggiore protezione
Conclusione
Questi studi indicano che l’utilizzo di vettori replicativi attenuati e non replicativi di HSV esprimenti la proteina Tat sono sicuri, in quanto non hanno mostrato effetti avversi durante gli esperimenti e al sacrificio. Questi risultati sono molto promettenti per lo sviluppo di una nuova generazione di vaccini efficaci HSV.

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Tipo di EPrint:Tesi di dottorato
Relatore:Caputo, Antonella
Dottorato (corsi e scuole):Ciclo 24 > Scuole 24 > BIOMEDICINA
Data di deposito della tesi:27 Gennaio 2012
Anno di Pubblicazione:27 Gennaio 2012
Parole chiave (italiano / inglese):Vaccini, Vettori, Tat proteina, immunizzazioni Vaccine, Vectors, Tat protein, immunization
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/19 Microbiologia generale
Struttura di riferimento:Dipartimenti > pre 2012 Dipartimento di Istologia, Microbiologia e Biotecnologie Mediche
Codice ID:4631
Depositato il:07 Nov 2012 11:51
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Bibliografia

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- Murray PR, Rosenthal KS, Kobayashi GS, Pfaller MA,. “ Microbiologia “EdiSES Napoli. 2002. Cerca con Google

2- La placa “ Principi di Microbiologia Medica” Nona Edizione; Società Editrice Esculapio, Bologna. 2001. Cerca con Google

3- Roizman B, Sears AE,. Herpes Simplex Viruses and their replication. In Fields BN, Knipe DM, Howley PM, Fields Virology. 1996 . Cerca con Google

4- Spear PG,. Entry of a herpes viruses into cells. Semin Virol. 1993. Cerca con Google

5- Batterson W, Roizman B,. Characterization of the Herpes Simplex virion-associated factor responsible for the induction of a gene. J. Virol. 1983. Cerca con Google

6- Kwong AD, Frenkel N,. The HSV virion host shut-off function. J. Virol. 1989. Cerca con Google

7- Laquerre S, Argnani R, Anderson DB, Zucchini S, Manservigi R, Glorioso JC. Heparan Sulphate proteoglycanbinding by herpes simplex virus type 1 glicoprotein B and C, which differ in their contribution to virus attachment, penetration, and cell-to-cell spread. J. Virol. 1998. Cerca con Google

8- Shukla D, Liu J, Blaiklock P, Shworak NW, Bai X, Esko JD, Cohen GH, Eisenberg RJ, Rosenberg RD, Spear PG,. A novel role for 3-O-Sulfated heparin sulphate in herpes simplex virus 1 entry. Cell. 1999. Cerca con Google

9- Campadelli-Fiume G, Amasio M, Avitabile E, Cerretani A, Forghieri C, Gianni T, Menotti L,. The multipartite system the mediates entry of herpes simplex virus into the cell. Rev. Med. Virol. 2007. Cerca con Google

10- Ogita H, Takai Y,. Nectins and nectin-like molecules: role in cell adhesion, polarization, movement and proliferation. IUBMB life. 2006. Cerca con Google

11- Menotti L, Cerretani A, Campadelli-Fiume G,. A Herpes Simplex recombinant that exibits a single-chain antibody to HER2/neu enters cells the mammary tumor receptor, independently of the gD receptor, J.Virol. 2006. Cerca con Google

12- Campadelli-Fiume G, Gianni T,. HSV glycoproteins and their roles in virus entry and eggress. In Alpha Herpesvirus Molecular and Cellular Biology. 2006. Cerca con Google

13- Christenson B, Esmark A,. Long-term follow studies on herpes simplex antibodies in the couse of cervical cancer: Patterns of neutralizing antibodies. Am. J. Epidemiol. 1971. Cerca con Google

14- Roizman B,. Fields Virology. Cerca con Google

15- Sacks SL, Griffiths PD, Corey L, Cohen C, Cunningham A, Dusheiko GM, Self S, Spruance S, Stanberry LR, Wald A, Whitley RJ,. (Herpes Simplex Virus) HSV shedding. Antiviral Res. 2004. Cerca con Google

16- Spruance SL, Overall JC Jr, Kern ER, Krueger GG, Pliam V, Miller W,. The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. N Engl J Med. 1977. Cerca con Google

17- Ramsey PG, Fife KH, Hackman RC, Meyers JD, Corey L,. Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients. Ann Intern Med. 1982. Cerca con Google

18- Suligoi B, Torri A, Grilli G, Tanzi E, PalĂş G,. Seroprevalence and seroincidence of herpes simplex virus type 1 and herpes simplex virus type 2 infections in a cohort of adolescents in Italy. Italian Herpes Management Forum. Sex Transm Dis. 2004. Cerca con Google

19- Dunn JR, Walker JD, Graham J, Weiss CB,. Gender differences in the relationship between housing, socioeconomic status, and self-reported health status. Rev Environ Health. 2000. Cerca con Google

20- Hayward GS., Jacob RJ., Wadsworth SC., and Roizman B,. Proc. Natd.Acad. Sc. USA. 1975. Cerca con Google

21- Vyse AJ, Gay NJ, Slomka MJ, Gopal R, Gibbs T, Morgan-Capner P, Brown DW,. The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes. Sex Transm Infect. 2000. Cerca con Google

22- Benedetti JK, Zeh J, Corey L,. Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time. Ann Intern Med. 1999. Cerca con Google

23- Madkan VK, Giancola AA, Sra KK, Tyring SK. Sex differences in the transmission, prevention, and disease manifestations of sexually transmitted diseases. Arch Dermatol. 2006. Cerca con Google

24- Roest RW, Carman WF, Maertzdorf J, Scoular A, Harvey J, Kant M, Van Der Meijden WI, Verjans GM, Osterhaus AD,. Genotypic analysis of sequential genital herpes simplex virus type 1 (HSV-1) isolates of patients with recurrent HSV-1 associated genital herpes. J Med Virol. 2004. Cerca con Google

25- Thapa M, Welner RS, Pelayo R, Carr DJ. CXCL9 and CXCL10 expression are critical for control of genital herpes simplex virus type 2 infection through mobilization of HSV-specific CTL and NK cells to the nervous systemJ Immunol. 2008. Cerca con Google

26- Murdoch C, Finn A. Chemokine receptors and their role in inflammation and infectious diseases. Blood. 2000. Cerca con Google

27- Liu MT, Chen BP, Oertel P, Buchmeier MJ, Armstrong D, Hamilton TA, Lane TE,. The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease. J Immunol. 2000. Cerca con Google

28- Kolb SA, Sporer B, Lahrtz F, Koedel U, Pfister HW, Fontana A. Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1 infected individuals as interferon- inducible protein 10. J Neuroimmunol. 1999. Cerca con Google

29- Liu MT, Armstrong D, Hamilton TA, Lane TE,. Expression of Mig (monokine induced by interferon-y) is important in T lymphocyte recruitment and host defense following viral infection of central nervous system. J Immunol. 2001. Cerca con Google

30- Thapa M, Welner RS, Pelayo R, Carr DJ,. CXCL9 and CXCL10 expression are critical for control of genital herpes simplex virus type 2 infection through mobilization of HSV-specific CTL and NK cells to the nervous system. J. Immunol. 2008. Cerca con Google

31- Murdoch C, Finn A. Chemokine receptors and their role in inflammation and infectious diseases. Blood. 2000. Cerca con Google

32- Liu MT, Chen BP, Oertel P, Buchmeier MJ, Armstrong D, Hamilton TA, Lane TE,. The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease. J. Immunol. 2000. Cerca con Google

33- Kolb SA, Sporer B, Lahrtz F, Koedel U, Pfister HW, Fontana A,. Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1 infected individuals as interferon- inducible protein 10. J. Neuroimmunol. 1999. Cerca con Google

34- Liu MT, Armstrong D, Hamilton TA, Lane TE,. Expression of Mig (monokine induced by interferon-y) is important in T lymphocyte recruitment and host defense following viral infection of central nervous system. J. Immunol. 2001. Cerca con Google

35- Christensen JE, Lemos CD, Moos T, Christensen JP, Thomsen AR,. CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system. J. Immunol. 2006. Cerca con Google

36- Ghersa P, Gelati M, Colinge J, Feger G, Power C, Papoin R, Salmaggi A,. MIG-differential gene expression in mouse brain endothelial cells. Neuroreport. 2002. Cerca con Google

37- Whitley RJ, Roizman B,. Herpes simplex viruses: is a vaccine tenable? J Clin Invest. 2002. Cerca con Google

38- Christensen JE, Lemos CD, Moos T, Christensen JP, Thomsen AR,. CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system. J. Immunol. 2006. Cerca con Google

39- Ghersa P, Gelati M, Colinge J, Feger G, Power C, Papoin R, Salmaggi A,. MIG-differential gene expression in mouse brain endothelial cells. Neuroreport. 2002 Cerca con Google

40- Koelle DM, Corey L,. Recent progress in herpes simplex virus immunobiology and vaccine research. Clin Microbiol Rev. 2003. Cerca con Google

41- Mertz G. J. G, Peterman R, Ashley, J. L, Jourden D. Salter, L. Morrison A. McLean, L Corey,. Herpes simplex virus type-2 glycoprotein-subunit vaccine: tolerance and humoral and cellular responses in humans. J. Infect. Dis.1984. Cerca con Google

42- Skinner G. R. B, M. E. Turyk, C. A. Benson, G. D. Wilbanks, P. Heseltine, J. Galpin, R. Kaufman, L. Goldberg, C. E. Hartley, A. Buchan. The efficacy and safety of Skinner herpes simplex vaccine towards modulation of herpes genitalis; report of a prospective double-blind placebo-controlled trail. Med. Microbiol. Immunol. 1997. Cerca con Google

43- Lachmann Robin H,. Herpes simplex virus-based vectors Int. J. Exp. Path. 2004. Cerca con Google

44- Shah AC, Benos D, Gillespie GY, Markert JM,. Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. J. Neurooncol.2003. Cerca con Google

45- Marconi P, Krisky D, Oligino T, Poliani PL, Ramakrishnan R, Goins WF, Fink DJ, Glorioso JC,. Replication-defective herpes simplex virus vectors for gene transfer in vivo. Proc Natl Acad Sci U S A. 1996. Cerca con Google

46- Goins WF, Marconi P, Krisky D, Wolfe D, Glorioso JC, Ramakrishnan R, Fink DJ,. Construction of replication-defective herpes simplex virus vectors. Curr Protoc Hum Genet. 2002. Cerca con Google

47- Bozac A, Berto E, Vasquez F, Grandi P, Caputo A, Manservigi R, Ensoli B, Marconi P,. Expression of human immunodeficiency virus type 1 tat from a replication-deficient herpes simplex type 1 vector induces antigen-specific T cell responses. Vaccine. 2006. Cerca con Google

48- Belshe RB, Leone PA, Bernstein DI, Wald A, Levin MJ, Stapleton JT, Gorfinkel I, Morrow RL, Ewell MG, Stokes-Riner A, Dubin G, Heineman TC, Schulte JM,. Efficacy results of a trial of a herpes simplex vaccine.N Engl J Med. 2012. Cerca con Google

49- Wang X, Xie G, Liao J, Yin D, Guan W, Pan M, Li J, Li Y,.Design and evaluation of a multi-epitope assembly peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice.Virol J. 2011. Cerca con Google

50- Bernstein DI, Harrison CJ, Jenski LJ, Myers MG, Stanberry LR,. Cell-mediated immunologic responses and recurrent genital herpes in the guinea pig. Effects of glycoprotein immunotherapy. J Immunol. 1991. Cerca con Google

51- Ott G, Barchfeld GL, Chernoff D, Radhakrishnan R, Van Hoogevest P, Van Nest G,.. Design and evaluation of a safe and potent adjuvant MF59 for human vaccines. Pharm Biotechnol. 1995. Cerca con Google

52- Pass RF, Duliegè AM, Boppana S, Sekulovich R, Percell S, Britt W, Burke RL,. A subunit cytomegalovirus vaccine based on recombinant envelope glycoprotein B and a new adjuvant. J Infect Dis. 1999. Cerca con Google

53- Heineman TC, Clements-Mann ML, Poland GA, Jacobson RM, Izu AE, Sakamoto D, Eiden J, Van Nest GA, Hsu HH,. A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant. Vaccine. 1999. Cerca con Google

54- Ott G, Barchfeld GL, Van Nest G. Enhancement of humoral response against human influenza vaccine with the simple submicron oil/water emulsion adjuvant MF59. Vaccine. 1995. Cerca con Google

55- Bernstein DI, Aoki FY, Tyring SK, Stanberry LR, St-Pierre C, Shafran SD, Leroux-Roels G, Van Herck K, Bollaerts A, Dubin G, GlaxoSmithKline,. Herpes Vaccine Study Group. Safety and immunogenicity of glycoprotein D-adjuvant genital herpes vaccine. Clin Infect Dis. 2005. Cerca con Google

56- Singh M, Carlson JR, Briones M, Ugozzoli M, Kazzaz J, Barackman J, Ott G, O'Hagan D,. A comparison of biodegradable microparticles and MF59 as systemic adjuvants for recombinant gD from HSV-2. Vaccine. 1998. Cerca con Google

57- Valensi J, Carlson M. J. R., Van Nest G,. Systemic cytokine profiles in Balb/c mice immunized with trivalent influenza vaccine containing MF59 oil emulsion and other advanced adjuvants. J. Immunol. 1994. Cerca con Google

58- Ott G, Van Nest G, Burke R. L.,. The use of muramyl peptides as vaccine adjuvants, p. 89-114. In E. Koff (ed.), Vaccine research: a series of advances, vol. 1. Marcel Dekker, New York, N.Y. 1991. Cerca con Google

59- Burke RL,. Contemporary approaches to vaccination against herpes simplex virus. Curr Top Microbiol Immunol. 1992. Cerca con Google

60- Stanberry LR,. Evaluation of herpes simplex virus vaccines in animals: the guinea pig vaginal model. Rev Infect Dis. 1991. Cerca con Google

61- Stanberry LR, Burke R, Myers MG,. Herpes simplex virus glycoprotein treatment of recurrent genital herpes. J Infect Dis. 1988. Cerca con Google

62- Straus, S. E, Corey L, Burke R. L., Savarese B, Barnum G., Krause P. R., Kost R. G., Meier J. L., Sekulovich R., Adair S. F., Dekker C. L,. Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet.1994. Cerca con Google

63- Straus S. E, Wald A, Kost R. G, McKenzie R, Langenberg A. G. M, Hohman P, Lekstrom J, Cox E, Nakamura M, Sekulovich R, Izu A, Dekker C, Corey L,. Immunotherapy of recurrent genital herpes with recombinant herpes simplex virua type 2 glycoproteins B and D: results of a placebo-controlled vaccine trial. J. Infect. Dis. 1997. Cerca con Google

64- Burke CJ, Hsu TA, Volkin DB,. Formulation, stability, and delivery of live attenuated vaccines for human use. Crit Rev Ther Drug Carrier Syst. 1999. Cerca con Google

65- Da Costa XJ, Bourne N, Stanberry LR, Knipe DM,. Construction and characterization of a replication-defective herpes simplex virus 2 ICP8 mutant strain and its use in immunization studies in a guinea pig model of genital disease. Virology. 1997. Cerca con Google

66- Epstein AL, Marconi P, Argnani R, Manservigi R,. HSV-1-derived recombinant and amplicon vectors for gene transfer and gene therapy. Curr Gene Ther. 2005. Cerca con Google

67- Manservigi R, Argnani R, Marconi P,. HSV Recombinant Vectors for Gene Therapy Open Virol J. 2010. Cerca con Google

68- Hill S, Zhang X, Boursnell ME, Shields JG, Ricciardi-Castagnoli P, Hickling JK,. Generation of a primary immune response to a genetically inactivated (DISC) herpes simplex virus and wild type virus. Biochem Soc Trans. 1997. Cerca con Google

69- Meignier B, Longnecker R, Roizman B,. In vivo behavior of genetically engineered herpes simplex viruses R7017 and R7020: construction and evaluation in rodents. J Infect Dis. 1988. Cerca con Google

70- Meignier B, Martin B, Whitley RJ, Roizman B,. In vivo behavior of genetically engineered herpes simplex viruses R7017 and R7020. Studies in immunocompetent and immunosuppressed owl monkeys. J Infect Dis. 1990. Cerca con Google

71- Whitley RJ, Kern ER, Chatterjee S, Chou J, Roizman B,. Replication, establishment of latency, and induced reactivation of herpes simplex virus gamma 1 34.5 deletion mutants in rodent models. J Clin Invest. 1993. Cerca con Google

72- Spivack JG, Fareed MU, Valyi-Nagy T, Nash TC, O'Keefe JS, Gesser RM, McKie EA, MacLean AR, Fraser NW, Brown SM,. Replication, establishment of latent infection, expression of the latency-associated transcripts and explant reactivation of herpes simplex virus type 1 gamma 34.5 mutants in a mouse eye model. J Gen Virol. 1995. Cerca con Google

73- Spector FC, Kern ER, Palmer J, Kaiwar R, Cha TA, Brown P, Spaete RR,. Evaluation of a live attenuated recombinant virus RAV 9395 as a herpes simplex virus type 2 vaccine in guinea pigs. J Infect Dis. 1998. Cerca con Google

74- Perng GC, Thompson RL, Sawtell NM, Taylor WE, Slanina SM, Ghiasi H, Kaiwar R, Nesburn AB, Wechsler SL,. An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. J Virol. 1995. Cerca con Google

75- Da Costa XJ, Jones CA, Knipe DM,. Immunization against genital herpes with a vaccine virus that has defects in productive and latent infection. Proc Natl Acad Sci U S A. 1999. Cerca con Google

76- De Bruyn Kops A, Uprichard SL, Chen M, Knipe DM,. Comparison of the intranuclear distributions of herpes simplex virus proteins involved in various viral functions. Virology. 1998. Cerca con Google

77- Boursnell ME, Entwisle C, Blakeley D, Roberts C, Duncan IA, Chisholm SE, Martin GM, Jennings R, Ni ChallanaĂ­n D, Sobek I, Inglis SC, McLean CS,. A genetically inactivated herpes simplex virus type 2 (HSV-2) vaccine provides effective protection against primary and recurrent HSV-2 disease. J Infect Dis. 1997. Cerca con Google

78- McLean CS, Erturk M, Jennings R, Challanain DN, Minson AC, Duncan I, Boursnell ME, Inglis SC,. Protective vaccination against primary and recurrent disease caused by herpes simplex virus (HSV) type 2 using a genetically disabled HSV-1. J Infect Dis. 1994. Cerca con Google

79- McLean CS, Ni Challanáin D, Duncan I, Boursnell ME, Jennings R, Inglis SC,. Induction of a protective immune response by mucosal vaccination with a DISC HSV-1 vaccine. Vaccine. 1996. Cerca con Google

80- Bravo FJ, Bourne N, Harrison CJ, Mani C, Stanberry LR, Myers MG, Bernstein DI,. Effect of antibody alone and combined with acyclovir on neonatal herpes simplex virus infection in guinea pigs. J Infect Dis. 1996. Cerca con Google

81- McClements WL, Armstrong ME, Keys RD, Liu MA,. Immunization with DNA vaccines encoding glycoprotein D or glycoprotein B, alone or in combination, induces protective immunity in animal models of herpes simplex virus-2 disease. Proc Natl Acad Sci U S A. 1996. Cerca con Google

82- Hu K, He X, Yu F, Yuan X, Hu W, Liu C, Zhao F, Dou J,. Immunization with DNA vaccine expressing herpes simplex virus type 1 gD and IL-21 protects against mouse herpes keratitis. Immunol Invest. 2011 Cerca con Google

83- Hu K, Dou J, Yu F, He X, Yuan X, Wang Y, Liu C, Gu N,. An ocular mucosal administration of nanoparticles containing DNA vaccine pRSC-gD-IL-21 confers protection against mucosal challenge with herpes simplex virus type 1 in mice. Vaccine. 2011. Cerca con Google

84- Fiorentini S, Marconi P, Avolio M, Marini E, Garrafa E, Caracciolo S, Rossi D, Bozac A, Becker PD, Gentili F, Facchetti F, Guzman CA, Manservigi R, Caruso A,. Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses. Microbes Infect. 2007. Cerca con Google

85- Berto E, Bozac A, Marconi P,. Development and application of replication-incompetent HSV-1-based vectors. Gene Ther. 2005. Cerca con Google

86- Advani SJ, Weichselbaum RR, Whitley RJ, Roizman B,. Friendly fire: redirecting herpes simplex virus-1 for therapeutic applications. Clin Microbiol Infect. 2002. Cerca con Google

87- Epstein AL,. HSV-1-derived recombinant and amplicon vectors for preventive or therapeutic gene transfer: an overview. Gene Ther. 2005. Cerca con Google

88- Kasai K, Saeki Y,. DNA-based methods to prepare helper virus-free herpes amplicon vectors and versatile design of amplicon vector plasmids. Curr Gene Ther. 2006. Cerca con Google

89- Santos K, Duke CM, Dewhurst S,. Amplicons as vaccine vectors. Curr Gene Ther. 2006. Cerca con Google

90- Chentoufi AA, Binder NR, Berka N, Durand G, Nguyen A, Bettahi I, Maillère B, BenMohamed L,. Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B. J Virol. 2008. Cerca con Google

91- Dasgupta G, Chentoufi AA, Nesburn AB, Wechsler SL, BenMohamed L,. New concepts in herpes simplex virus vaccine development: notes from the battlefield. Expert Rev Vaccines. 2009. Cerca con Google

92- Huilan Y, Cui Z, Jianyong F, Lei G, Wei Q,. Construction of, and T-helper (Th)1/Th2 immune responses to, a herpes simplex virus type 2 glycoprotein D-cytotoxic T-lymphocyte epitope DNA vaccine. Clin Exp Dermatol. 2010. Cerca con Google

93- Dupuis M, Denis-Mize K, LaBarbara A, Peters W, Charo IF, McDonald DM, Ott G,. Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis. Eur J Immunol. 2001. Cerca con Google

94- Singh M, Carlson JR, Briones M, Ugozzoli M, Kazzaz J, Barackman J, Ott G, O'Hagan D,. A comparison of biodegradable microparticles and MF59 as systemic adjuvants for recombinant gD from HSV-2. Vaccine. 1998. Cerca con Google

95- Gavioli R, Guerrini R, Masucci MG, Tomatis R, Traniello S, Marastoni M,. High structural side chain specificity required at the second position of immunogenic peptides to obtain stable MHC/peptide complexes. FEBS Lett. 1998. Cerca con Google

96- Kittiworakarn J, Lecoq A, Moine G, Thai R, Lajeunesse E, Drevet P, Vidaud C, MĂ©nez A, LĂ©onetti M,. HIV-1 Tat raises an adjuvant-free humoral immune response controlled by its core region and its ability to form cysteine-mediated oligomers. J Biol Chem. 2006. Cerca con Google

97- Ensoli B, Bellino S, Tripiciano A, Longo O, Francavilla V, Marcotullio S, Cafaro A, Picconi O, Paniccia G, Scoglio A, Arancio A, Ariola C, Ruiz Alvarez MJ, Campagna M, Scaramuzzi D, Iori C, Esposito R, Mussini C, Ghinelli F, Sighinolfi L, Palamara G, Latini A, Angarano G, Ladisa N, Soscia F, Mercurio VS, Lazzarin A, Tambussi G, Visintini R, Mazzotta F, Di Pietro M, Galli M, Rusconi S, Carosi G, Torti C, Di Perri G, Bonora S, Ensoli F, Garaci E,. Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART. PLoS One. 2010. Cerca con Google

98- Gavioli R, Cellini S, Castaldello A, Voltan R, Gallerani E, Gagliardoni F, Fortini C, Cofano EB, Triulzi C, Cafaro A, Srivastava I, Barnett S, Caputo A, Ensoli B,. The Tat protein broadens T cell responses directed to the HIV-1 antigens Gag and Env: implications for the design of new vaccination strategies against AIDS. Vaccine. 2008. Cerca con Google

99- Kronenberg K, Brosch S, Butsch F, Tada Y, Shibagaki N, Udey MC, von Stebut E,. Vaccination with TAT-antigen fusion protein induces protective, CD8(+) T cell-mediated immunity against Leishmania major. J Invest Dermatol. 2010. Cerca con Google

100- Caputo A, Brocca-Cofano E, Castaldello A, Voltan R, Gavioli R, Srivastava IK, Barnett SW, Cafaro A, Ensoli B,. Characterization of immune responses elicited in mice by intranasal co-immunization with HIV-1 Tat, gp140 DeltaV2Env and/or SIV Gag proteins and the nontoxicogenic heat-labile Escherichia coli enterotoxin. Vaccine. 2008. Cerca con Google

Kirman JR, Turon T, Su H, Li A, Kraus C, Polo JM., Belisle J, Morris S, Seader RA,. Enhanced immunogenicity to M.tuberculosis by vaccination with an alphavirus plasmid replicon expressing antigen 85A. Infect. Immun. 2003. 101- Cerca con Google

101- Glorioso JC, Goins WF, Schmidt MC, Oligino T, Krisky DM, Marconi PC, Cavalcoli JD, Ramakrishnan R, Poliani PL, Fink DJ,. Engineering herpes simplex virus vectors for human gene therapy. Adv Pharmacol. 1997. Cerca con Google

102- Arya SK, Guo C, Josephs SF, Wong-Staal F.Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985. Cerca con Google

103- Samady L, Costigliola E, MacCormac L, McGrath Y, Cleverley S, Lilley CE, Smith J, Latchman DS, Chain B, Coffin RS.Deletion of the virion host shutoff protein (vhs) from herpes simplex virus (HSV) relieves the viral block to dendritic cell activation: potential of vhs- HSV vectors for dendritic cell-mediated immunotherapy. J Virol. 2003 Cerca con Google

104- Doepker RC, Hsu WL, Saffran HA, Smiley JR.Herpes simplex virus virion host shutoff protein is stimulated by translation initiation factors eIF4B and eIF4H. J Virol. 2004 Cerca con Google

105- Cotter CR, Nguyen ML, Yount JS, LĂłpez CB, Blaho JA, Moran TM. The virion host shut-off (vhs) protein blocks a TLR-independent pathway of herpes simplex virus type 1 recognition in human and mouse dendritic cells. PLoS One. 2010 Cerca con Google

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