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Clinical and Developmental Immunology
Volume 2012, Article ID 187585, 16 pages
http://dx.doi.org/10.1155/2012/187585
Review Article

Towards a Rational Design of an Asymptomatic Clinical Herpes Vaccine: The Old, the New, and the Unknown

1Laboratory of Cellular and Molecular Immunology, School of Medicine, University of California, Irvine, Irvine, CA 92697-4375, USA
2Department of Immunology, Pathology and Clinical Laboratory Medicine, King Fahad Medical City, Riyadh 11525, Saudi Arabia
3Institute for Immunology, School of Medicine, University of California, Irvine, Irvine, CA 92697-4120, USA
4Chao Family Comprehensive Cancer Center, University of California, Irvine Medical Center, Irvine, CA 92868-3201, USA

Received 15 November 2011; Accepted 10 January 2012

Academic Editor: Philippe Van de Perre

Copyright © 2012 Aziz Alami Chentoufi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. B. Belshe, P. A. Leone, D. I. Bernstein et al., “Efficacy results of a trial of a herpes simplex vaccine,” The New England Journal of Medicine, vol. 366, pp. 34–43, 2012. View at Google Scholar
  2. A. A. Chentoufi and L. Benmohamed, “Future viral vectors for the delivery of asymptomatic herpes epitope-based immunotherapeutic vaccines,” Future Virology, vol. 5, no. 5, pp. 525–528, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. P. A. Rubbo, E. Tuaillon, N. Nagot et al., “HIV-1 infection impairs HSV-specific CD4+ and CD8+ T-cell response by reducing Th1 cytokines and CCR5 ligand secretion,” Journal of Acquired Immune Deficiency Syndromes, vol. 58, no. 1, pp. 9–17, 2011. View at Google Scholar
  4. X. Jiang, A. A. Chentoufi, C. Hsiang et al., “The herpes simplex virus type 1 latency-associated transcript can protect neuron-derived C1300 and neuro2A cells from granzyme B-induced apoptosis and CD8 T-cell killing,” Journal of Virology, vol. 85, no. 5, pp. 2325–2332, 2011. View at Publisher · View at Google Scholar
  5. G. Dasgupta, A. A. Chentoufi, S. You et al., “Engagement of TLR2 reverses the suppressor function of conjunctiva CD4+CD25+ regulatory T cells and promotes herpes simplex virus epitope-specific CD4+CD25- effector T cell responses,” Investigative Ophthalmology & Visual Science, vol. 52, no. 6, pp. 3321–3333, 2011. View at Google Scholar
  6. A. A. Chentoufi, E. Kritzer, M. V. Tran et al., “The herpes simplex virus 1 latency-associated transcript promotes functional exhaustion of virus-specific CD8+ T cells in latently infected trigeminal ganglia: a novel immune evasion mechanism,” Journal of Virology, vol. 85, no. 17, pp. 9127–9138, 2011. View at Publisher · View at Google Scholar
  7. L. R. Stanberry, A. L. Cunningham, A. Mindel et al., “Prospects for control of herpes simplex virus disease through immunization,” Clinical Infectious Diseases, vol. 30, no. 3, pp. 549–566, 2000. View at Publisher · View at Google Scholar · View at Scopus
  8. D. M. Koelle, Z. Liu, C. L. McClurkan et al., “Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 22, pp. 12899–12904, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. D. M. Koelle and L. Corey, “Recent progress in herpes simplex virus immunobiology and vaccine research,” Clinical Microbiology Reviews, vol. 16, no. 1, pp. 96–113, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. D. M. Koelle, “Expression cloning for the discovery of viral antigens and epitopes recognized by T cells,” Methods, vol. 29, no. 3, pp. 213–226, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Cohen, “Painful failure of promising genital herpes vaccine,” Science, vol. 330, no. 6002, p. 304, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. G. Dasgupta, A. A. Chentoufi, A. B. Nesburn, S. L. Wechsler, and L. BenMohamed, “New concepts in herpes simplex virus vaccine development: notes from the battlefield,” Expert Review of Vaccines, vol. 8, no. 8, pp. 1023–1035, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. D. M. Koelle and L. Corey, “Herpes simplex: insights on pathogenesis and possible vaccines,” Annual Review of Medicine, vol. 59, pp. 381–395, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. J. E. Knickelbein, R. L. Hendricks, and P. Charukamnoetkanok, “Management of herpes simplex virus stromal keratitis: an evidence-based review,” Survey of Ophthalmology, vol. 54, no. 2, pp. 226–234, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. Yuki and H. Kiyono, “Mucosal vaccines: novel advances in technology and delivery,” Expert Review of Vaccines, vol. 8, no. 8, pp. 1083–1097, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. H. Weiss, “Epidemiology of herpes simplex virus type 2 infection in the developing world,” Herpes, vol. 11, supplement 1, pp. 24A–35A, 2004. View at Google Scholar · View at Scopus
  17. A. G. M. Langenberg, L. Corey, R. L. Ashley, W. P. Leong, and S. E. Straus, “A prospective study of new infections with herpes simplex virus type 1 and type 2,” New England Journal of Medicine, vol. 341, no. 19, pp. 1432–1438, 1999. View at Publisher · View at Google Scholar
  18. R. Whitley, “Neonatal herpes simplex virus infection,” Current Opinion in Infectious Diseases, vol. 17, no. 3, pp. 243–246, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. F. Taboulet, B. Halioua, and J. E. Malkin, “Quality of life and use of health care among people with genital herpes in France,” Acta Dermato-Venereologica, vol. 79, no. 5, pp. 380–384, 1999. View at Publisher · View at Google Scholar · View at Scopus
  20. L. Corey, A. Wald, C. L. Celum, and T. C. Quinn, “The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics,” Journal of Acquired Immune Deficiency Syndromes, vol. 35, no. 5, pp. 435–445, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. C. Danve-Szatanek, M. Aymard, D. Thouvenot et al., “Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up,” Journal of Clinical Microbiology, vol. 42, no. 1, pp. 242–249, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Fonnest, I. De La Fuente Fonnest, and T. Weber, “Neonatal herpes in Denmark 1977–1991,” Acta Obstetricia et Gynecologica Scandinavica, vol. 76, no. 4, pp. 355–358, 1997. View at Google Scholar
  23. C. A. Jones, M. Fernandez, K. Herc et al., “Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro,” Journal of Virology, vol. 77, no. 20, pp. 11139–11149, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Dasgupta and L. BenMohamed, “Of mice and not humans: how reliable are animal models for evaluation of herpes CD8+-T cell-epitopes-based immunotherapeutic vaccine candidates?” Vaccine, vol. 29, no. 35, pp. 5824–5836, 2011. View at Publisher · View at Google Scholar
  25. S. J. Allen, K. R. Mott, A. A. Chentoufi et al., “CD11c controls Herpes Simplex Virus 1 responses to limit virus replication during primary infection,” Journal of Virology, vol. 85, no. 19, pp. 9945–9955, 2011. View at Publisher · View at Google Scholar
  26. S. J. Allen, P. Hamrah, D. Gate et al., “The role of LAT in increased CD8+ T cell exhaustion in trigeminal ganglia of mice latently infected with herpes simplex virus 1,” Journal of Virology, vol. 85, no. 9, pp. 4184–4197, 2011. View at Publisher · View at Google Scholar
  27. J. Thomas and B. T. Rouse, “Immunopathogenesis of herpetic ocular disease,” Immunologic Research, vol. 16, no. 4, pp. 375–386, 1997. View at Google Scholar · View at Scopus
  28. Y. Osorio, J. Cohen, and H. Ghiasi, “Improved protection from primary ocular HSV-1 infection and establishment of latency using multigenic DNA vaccines,” Investigative Ophthalmology and Visual Science, vol. 45, no. 2, pp. 506–514, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. D. J. J. Carr, P. Härle, and B. M. Gebhardt, “The immune response to ocular herpes simplex virus type 1 infection,” Experimental Biology and Medicine, vol. 226, no. 5, pp. 353–366, 2001. View at Google Scholar · View at Scopus
  30. S. Deshpande, M. Zheng, S. Lee et al., “Bystander activation involving T lymphocytes in herpetic stromal keratitis,” Journal of Immunology, vol. 167, no. 5, pp. 2902–2910, 2001. View at Google Scholar · View at Scopus
  31. K. S. Rosenthal, H. Mao, W. I. Horne, C. Wright, and D. Zimmerman, “Immunization with a LEAPS(TM) heteroconjugate containing a CTL epitope and a peptide from beta-2-microglobulin elicits a protective and DTH response to herpes simplex virus type 1,” Vaccine, vol. 17, no. 6, pp. 535–542, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. G. Dasgupta, A. B. Nesburn, S. L. Wechsler, and L. BenMohamed, “Editorial: developing an asymptomatic mucosal herpes vaccine: the present and the future,” Future Microbiology, vol. 5, no. 1, pp. 1–4, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. A. A. Chentoufi, G. Dasgupta, A. B. Nesburn et al., “Nasolacrimal duct closure modulates ocular mucosal and systemic CD4+ T-cell responses induced following topical ocular or intranasal immunization,” Clinical and Vaccine Immunology, vol. 17, no. 3, pp. 342–353, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. A. A. Chentoufi, G. Dasgupta, N. D. Christensen et al., “A novel HLA (HLA-A*0201) transgenic rabbit model for preclinical evaluation of human CD8+ T cell epitope-based vaccines against ocular herpes,” Journal of Immunology, vol. 184, no. 5, pp. 2561–2571, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. N. Dejucq and B. Jégou, “Viruses in the mammalian male genital tract and their effects on the reproductive system,” Microbiology and Molecular Biology Reviews, vol. 65, no. 2, pp. 208–231, 2001. View at Publisher · View at Google Scholar
  36. M. A. Tigges, D. Koelle, K. Hartog, R. E. Sekulovich, L. Corey, and R. L. Burke, “Human CD8+ herpes simplex virus-specific cytotoxic T-lymphocyte clones recognize diverse virion protein antigens,” Journal of Virology, vol. 66, no. 3, pp. 1622–1634, 1992. View at Google Scholar · View at Scopus
  37. L. R. Stanberry, “Evaluation of herpes simplex virus vaccines in animals: the guinea pig vaginal model,” Reviews of Infectious Diseases, vol. 13, no. 11, pp. S920–S923, 1991. View at Google Scholar · View at Scopus
  38. D. I. Bernstein and L. R. Stanberry, “Herpes simplex virus vaccines,” Vaccine, vol. 17, no. 13-14, pp. 1681–1689, 1999. View at Publisher · View at Google Scholar · View at Scopus
  39. L. R. Stanberry, “Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines,” Herpes, vol. 11, 3, pp. 161A–169A, 2004. View at Google Scholar · View at Scopus
  40. Y. Hoshino, S. K. Dalai, K. Wang et al., “Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs,” Journal of Virology, vol. 79, no. 1, pp. 410–418, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. M. E. G. Boursnell, C. Entwisle, S. A. Ali et al., “Disabled infectious single cycle (disc) herpes simplex virus as a vector for immunotherapy of cancer,” Advances in Experimental Medicine and Biology, vol. 451, pp. 379–384, 1998. View at Google Scholar · View at Scopus
  42. X. Zhang, M. De Alwis, S. L. Hart et al., “High-titer recombinant adeno-associated virus production from replicating amplicons and herpes vectors deleted for glycoprotein H,” Human Gene Therapy, vol. 10, no. 15, pp. 2527–2537, 1999. View at Publisher · View at Google Scholar · View at Scopus
  43. G. P. Garnett, G. Dubin, M. Slaoui, and T. Darcis, “The potential epidemiological impact of a genital herpes vaccine for women,” Sexually Transmitted Infections, vol. 80, no. 1, pp. 24–29, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. S. M. Swetter, E. L. Hill, E. R. Kern et al., “Chronic vulvar ulceration in an immunocompetent woman due to acyclovir- resistant, thymidine kinase-deficient herpes simplex virus,” Journal of Infectious Diseases, vol. 177, no. 3, pp. 543–550, 1998. View at Google Scholar · View at Scopus
  45. F. C. Spector, E. R. Kern, J. Palmer et al., “Evaluation of a live attenuated recombinant virus RAV 9395 as a herpes simplex virus type 2 vaccine in guinea pigs,” Journal of Infectious Diseases, vol. 177, no. 5, pp. 1143–1154, 1998. View at Google Scholar · View at Scopus
  46. F. J. Branco and N. W. Fraser, “Herpes simplex virus type 1 latency-associated transcript expression protects trigeminal ganglion neurons from apoptosis,” Journal of Virology, vol. 79, no. 14, pp. 9019–9025, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Franchini, H. Hefti, S. Vollstedt et al., “Dendritic cells from mice neonatally vaccinated with modified vaccinia virus ankara transfer resistance against herpes simplex virus type I to naive one-week-old mice,” Journal of Immunology, vol. 172, no. 10, pp. 6304–6312, 2004. View at Google Scholar · View at Scopus
  48. C. Abril, M. Engels, A. Liman et al., “Both viral and host factors contribute to neurovirulence of bovine herpesviruses 1 and 5 in interferon receptor-deficient mice,” Journal of Virology, vol. 78, no. 7, pp. 3644–3653, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Franchini, C. Abril, C. Schwerdel, C. Ruedl, M. Ackermann, and M. Suter, “Protective T-cell-based immunity induced in neonatal mice by a single replicative cycle of herpes simplex virus,” Journal of Virology, vol. 75, no. 1, pp. 83–89, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Ghiasi, S. Cai, S. Slanina, A. B. Nesburn, and S. L. Wechsler, “Vaccination of mice with herpes simplex virus type 1 glycoprotein D DNA produces low levels of protection against lethal HSV-1 challenge,” Antiviral Research, vol. 28, no. 2, pp. 147–157, 1995. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Manservigi, A. Boero, R. Argnani et al., “Immunotherapeutic activity of a recombinant combined gB-gD-gE vaccine against recurrent HSV-2 infections in a guinea pig model,” Vaccine, vol. 23, no. 7, pp. 865–872, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. N. A. Hosken, “Development of a therapeutic vaccine for HSV-2,” Vaccine, vol. 23, no. 17-18, pp. 2395–2398, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. L. R. Stanberry, S. L. Spruance, A. L. Cunningham et al., “Glycoprotein-D-adjuvant vaccine to prevent genital herpes,” New England Journal of Medicine, vol. 347, no. 21, pp. 1652–1661, 2002. View at Publisher · View at Google Scholar · View at Scopus
  54. N. Hosken, P. McGowan, A. Meier et al., “Diversity of the CD8+ T-cell response to herpes simplex virus type 2 proteins among persons with genital herpes,” Journal of Virology, vol. 80, no. 11, pp. 5509–5515, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Rajčáni and V. Ďurmanová, “Developments in herpes simplex virus vaccines: old problems and new challenges,” Folia Microbiologica, vol. 51, no. 2, pp. 67–85, 2006. View at Publisher · View at Google Scholar
  56. D. M. Koelle, “Vaccines for herpes simplex virus infections,” Current Opinion in Investigational Drugs, vol. 7, no. 2, pp. 136–141, 2006. View at Google Scholar · View at Scopus
  57. A. Wald, L. Corey, R. Cone, A. Hobson, G. Davis, and J. Zeh, “Frequent genital herpes simplex virus 2 shedding in immunocompetent women: effect of acyclovir treatment,” Journal of Clinical Investigation, vol. 99, no. 5, pp. 1092–1097, 1997. View at Google Scholar · View at Scopus
  58. B. Knaup, S. Schünemann, and M. H. Wolff, “Subclinical reactivation of herpes simplex virus type 1 in the oral cavity,” Oral Microbiology and Immunology, vol. 15, no. 5, pp. 281–283, 2000. View at Google Scholar · View at Scopus
  59. A. Wald, J. Zeh, S. Selke et al., “Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons,” New England Journal of Medicine, vol. 342, no. 12, pp. 844–850, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Wald, J. Zeh, S. Selke, T. Warren, R. Ashley, and L. Corey, “Genital shedding of herpes simplex virus among men,” Journal of Infectious Diseases, vol. 186, no. 1, pp. S34–S39, 2002. View at Publisher · View at Google Scholar · View at Scopus
  61. K. R. Wilhelmus, R. W. Beck, P. S. Moke et al., “Acyclovir for the prevention of recurrent herpes simplex virus eye disease,” New England Journal of Medicine, vol. 339, no. 5, pp. 300–306, 1998. View at Publisher · View at Google Scholar
  62. J. F. Leigh, N. Acharya, V. Cevallos, and T. P. Margolis, “Does asymptomatic shedding of herpes simplex virus on the ocular surface lead to false-positive diagnostic PCR results?” British Journal of Ophthalmology, vol. 92, no. 3, pp. 435–436, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. M. L. Freeman, B. S. Sheridan, R. H. Bonneau, and R. L. Hendricks, “Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections,” Journal of Immunology, vol. 179, no. 1, pp. 322–328, 2007. View at Google Scholar · View at Scopus
  64. E. Tronstein, C. Johnston, M.-L. Huang et al., “Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection,” Journal of the American Medical Association, vol. 305, no. 14, pp. 1441–1449, 2011. View at Publisher · View at Google Scholar
  65. H. E. Kaufman, A. M. Azcuy, E. D. Varnell, G. D. Sloop, H. W. Thompson, and J. M. Hill, “HSV-1 DNA in tears and saliva of normal adults,” Investigative Ophthalmology and Visual Science, vol. 46, no. 1, pp. 241–247, 2005. View at Publisher · View at Google Scholar · View at Scopus
  66. T. J. Liesegang, “Herpes simplex virus epidemiology and ocular importance,” Cornea, vol. 20, no. 1, pp. 1–13, 2001. View at Publisher · View at Google Scholar · View at Scopus
  67. A. A. Chentoufi, N. R. Binder, N. Berka et al., “Asymptomatic human CD4+ cytotoxic T-cell epitopes identified from herpes simplex virus glycoprotein B,” Journal of Virology, vol. 82, no. 23, pp. 11792–11802, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. L. Corey, A. G.M. Langenberg, R. Ashley et al., “Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials,” Journal of the American Medical Association, vol. 282, no. 4, pp. 331–340, 1999. View at Publisher · View at Google Scholar
  69. H. M. Friedman, C. Hartley, L. Corey et al., “Immunologic strategies for herpes vaccination,” Journal of the American Medical Association, vol. 283, no. 6, pp. 746–747, 2000. View at Google Scholar · View at Scopus
  70. M. A. Brehm, A. K. Pinto, K. A. Daniels, J. P. Schneck, R. M. Welsh, and L. K. Selin, “T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens,” Nature Immunology, vol. 3, no. 7, pp. 627–634, 2002. View at Publisher · View at Google Scholar · View at Scopus
  71. H. D. Chen, A. E. Fraire, I. Joris, M. A. Brehm, R. M. Welsh, and L. K. Selin, “Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung,” Nature Immunology, vol. 2, no. 11, pp. 1067–1076, 2001. View at Publisher · View at Google Scholar · View at Scopus
  72. S. K. Kim, M. A. Brehm, R. M. Welsh, and L. K. Selin, “Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation,” Journal of Immunology, vol. 169, no. 1, pp. 90–98, 2002. View at Google Scholar · View at Scopus
  73. K. Eriksson, L. Bellner, S. Görander et al., “CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals,” Journal of General Virology, vol. 85, no. 8, pp. 2139–2147, 2004. View at Publisher · View at Google Scholar
  74. A. A. Chentoufi, X. Zhang, K. Lamberth et al., “HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D,” Journal of Immunology, vol. 180, no. 1, pp. 426–437, 2008. View at Google Scholar · View at Scopus
  75. X. Zhang, F. A. Castelli, X. Zhu, M. Wu, B. Maillère, and L. BenMohamed, “Gender-dependent HLA-DR-restricted epitopes identified from herpes simplex virus type 1 glycoprotein D,” Clinical and Vaccine Immunology, vol. 15, no. 9, pp. 1436–1449, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. J. E. Blaney, E. Nobusawa, M. A. Brehm et al., “Immunization with a single major histocompatibility complex class I- restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity,” Journal of Virology, vol. 72, no. 12, pp. 9567–9574, 1998. View at Google Scholar · View at Scopus
  77. X. Zhang, A. A. Chentoufi, G. Dasgupta et al., “A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge,” Mucosal Immunology, vol. 2, no. 2, pp. 129–143, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. I. Bettahi, A. B. Nesburn, S. Yoon et al., “Protective immunity against ocular herpes infection and disease induced by highly immunogenic self-adjuvanting glycoprotein D lipopeptide vaccines,” Investigative Ophthalmology and Visual Science, vol. 48, no. 10, pp. 4643–4653, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. A. Sette, E. Keogh, G. Ishioka et al., “Epitope identification and vaccine design for cancer immunotherapy,” Current Opinion in Investigational Drugs, vol. 3, no. 1, pp. 132–139, 2002. View at Google Scholar · View at Scopus
  80. A. Sette, M. Newman, B. Livingston et al., “Optimizing vaccine design for cellular processing, MHC binding and TCR recognition,” Tissue Antigens, vol. 59, no. 6, pp. 443–451, 2002. View at Publisher · View at Google Scholar · View at Scopus
  81. H. Gahéry-Ségard, G. Pialoux, S. Figueiredo et al., “Long-term specific immune responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine: characterization of CD8+-T-cell epitopes recognized,” Journal of Virology, vol. 77, no. 20, pp. 11220–11231, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. G. Pialoux, H. Gahéry-Ségard, S. Sermet et al., “Lipopeptides induce cell-mediated anti-HIV immune responses in seronegative volunteers,” AIDS, vol. 15, no. 10, pp. 1239–1249, 2001. View at Publisher · View at Google Scholar · View at Scopus
  83. C. Klinguer, D. David, M. Kouach et al., “Characterization of a multi-lipopeptides mixture used as an HIV-1 vaccine candidate,” Vaccine, vol. 18, no. 3-4, pp. 259–267, 1999. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Hilbert, F. Hudecz, G. Mezo et al., “The influence of branched polypeptide carriers on the immunogenicity of predicted epitopes of HSV-1 glycoprotein D,” Scandinavian Journal of Immunology, vol. 40, no. 6, pp. 609–617, 1994. View at Publisher · View at Google Scholar
  85. G. Schlecht, J. Loucka, H. Najar, P. Sebo, and C. Leclerc, “Antigen targeting to CD11b allows efficient presentation of CD4+ and CD8+ T cell epitopes and in vivo Th1-polarized T cell priming,” Journal of Immunology, vol. 173, no. 10, pp. 6089–6097, 2004. View at Google Scholar · View at Scopus
  86. P. Rueda, G. Morón, J. Sarraseca, C. Leclerc, and J. I. Casal, “Influence of flanking sequences on presentation efficiency of a CD8+ cytotoxic T-cell epitope delivered by parvovirus-like a particles,” Journal of General Virology, vol. 85, no. 3, pp. 563–572, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. X. Jiao, R. Lo-Man, N. Winter, E. Dériaud, B. Gicquel, and C. Leclerc, “The shift of Th1 to Th2 immunodominance associated with the chronicity of Mycobacterium bovis bacille Calmette-Guérin infection does not affect the memory response,” Journal of Immunology, vol. 170, no. 3, pp. 1392–1398, 2003. View at Google Scholar · View at Scopus
  88. C. Sedlik, E. Dériaud, and C. Leclerc, “Lack of T(h)1 or T(h)2 polarization of CD4+ T cell response induced by particulate antigen targeted to phagocytic cells,” International Immunology, vol. 9, no. 1, pp. 91–103, 1997. View at Publisher · View at Google Scholar · View at Scopus
  89. Y. Osorio, B. G. Sharifi, G. C. Perng, N. S. Ghiasi, and H. Ghiasi, “The role of TH1 and TH2 cytokines in HSV-1-induced corneal scarring,” Ocular Immunology and Inflammation, vol. 10, no. 2, pp. 105–116, 2002. View at Publisher · View at Google Scholar · View at Scopus
  90. P. Daubersies, A. W. Thomas, P. Millet et al., “Protection against Plasmodium falciparum malaria in chimpanzees by immunization with the conserved pre-erythrocytic liver-stage antigen 3,” Nature Medicine, vol. 6, no. 11, pp. 1258–1263, 2000. View at Publisher · View at Google Scholar · View at Scopus
  91. L. BenMohamed, A. Thomas, and P. Druilhe, “Long-term multiepitopic cytotoxic-T-lymphocyte responses induced in chimpanzees by combinations of Plasmodium falciparum liver-stage peptides and lipopeptides,” Infection and Immunity, vol. 72, no. 8, pp. 4376–4384, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. R. Lo-Man, S. Vichier-Guerre, R. Perraut et al., “A fully synthetic therapeutic vaccine candidate targeting carcinoma-associated Tn carbohydrate antigen induces tumor-specific antibodies in nonhuman primates,” Cancer Research, vol. 64, no. 14, pp. 4987–4994, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Vichier-Guerre, R. Lo-Man, V. Huteau, E. Dériaud, C. Leclerc, and S. Bay, “Synthesis and immunological evaluation of an antitumor neoglycopeptide vaccine bearing a novel homoserine Tn antigen,” Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 13, pp. 3567–3570, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. X. Zhu, T. V. Ramos, H. Gras-Masse, B. E. Kaplan, and L. BenMohamed, “Lipopeptide epitopes extended by an NE-palmitoyl-lysine moiety increase uptake and maturation of dendritic cells through a Toll-like receptor-2 pathway and trigger a Th1-dependent protective immunity,” European Journal of Immunology, vol. 34, no. 5, pp. 1142–1149, 2004. View at Google Scholar
  95. G. N. Milligan, D. I. Bernstein, and N. Bourne, “T lymphocytes are required for protection of the vaginal mucosae and sensory ganglia of immune mice against reinfection with herpes simplex virus type 2,” Journal of Immunology, vol. 160, no. 12, pp. 6093–6100, 1998. View at Google Scholar · View at Scopus
  96. N. A. Kuklin, M. Daheshia, S. Chun, and B. T. Rouse, “Role of mucosal immunity in herpes simplex virus infection,” Journal of Immunology, vol. 160, no. 12, pp. 5998–6003, 1998. View at Google Scholar · View at Scopus
  97. L. BenMohamed, Y. Belkaid, E. Loing, K. Brahimi, H. Gras-Masse, and P. Druilhe, “Systemic immune responses induced by mucosal administration of lipopeptides without adjuvant,” European Journal of Immunology, vol. 32, no. 8, pp. 2274–2281, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. L. BenMohamed, R. Krishnan, C. Auge, J. F. Primus, and D. J. Diamond, “Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses,” Immunology, vol. 106, no. 1, pp. 113–121, 2002. View at Publisher · View at Google Scholar · View at Scopus
  99. L. BenMohamed, S. L. Wechsler, and A. B. Nesburn, “Lipopeptide vaccines—yesterday, today, and tomorrow,” Lancet Infectious Diseases, vol. 2, no. 7, pp. 425–431, 2002. View at Publisher · View at Google Scholar · View at Scopus
  100. G. C. Perng, B. Maguen, L. Jin et al., “A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency-associated transcript produces a protein in infected rabbits,” Journal of Virology, vol. 76, no. 16, pp. 8003–8010, 2002. View at Publisher · View at Google Scholar · View at Scopus
  101. O. Renaudet, G. Dasgupta, I. Bettahi et al., “Linear and branched glyco-lipopeptide vaccines follow distinct cross-presentation pathways and generate different magnitudes of antitumor immunity,” PLoS ONE, vol. 5, no. 6, Article ID e11216, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. P. M. Moyle and I. Toth, “Self-adjuvanting lipopeptide vaccines,” Current Medicinal Chemistry, vol. 15, no. 5, pp. 506–516, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. K. R. Mott, C. J. Bresee, S. J. Allen, L. BenMohamed, S. L. Wechsler, and H. Ghiasi, “Level of herpes simplex virus type 1 latency correlates with severity of corneal scarring and exhaustion of CD8+ T cells in trigeminal ganglia of latently infected mice,” Journal of Virology, vol. 83, no. 5, pp. 2246–2254, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. K. R. Mott, A. A. Chentoufi, D. Carpenter, L. Benmohamed, S. L. Wechsler, and H. Ghiasi, “The role of a glycoprotein K (gK) CD8+T-Cell epitope of herpes simplex virus on virus replication and pathogenicity,” Investigative Ophthalmology and Visual Science, vol. 50, no. 6, pp. 2903–2912, 2009. View at Publisher · View at Google Scholar
  105. A. Hill, P. Juovic, I. York et al., “Herpes simplex virus turns off the TAP to evade host immunity,” Nature, vol. 375, no. 6530, pp. 411–415, 1995. View at Google Scholar · View at Scopus
  106. F. N. Toka, C. D. Pack, and B. T. Rouse, “Molecular adjuvants for mucosal immunity,” Immunological Reviews, vol. 199, pp. 100–112, 2004. View at Publisher · View at Google Scholar · View at Scopus
  107. P. Brandtzaeg and R. Pabst, “Let's go mucosal: communication on slippery ground,” Trends in Immunology, vol. 25, no. 11, pp. 570–577, 2004. View at Publisher · View at Google Scholar · View at Scopus
  108. J. P. Bouvet, N. Decroix, and P. Pamonsinlapatham, “Stimulation of local antibody production: parenteral or mucosal vaccination?” Trends in Immunology, vol. 23, no. 4, pp. 209–213, 2002. View at Publisher · View at Google Scholar · View at Scopus
  109. A. Hayday and J. L. Viney, “The ins and outs of body surface immunology,” Science, vol. 290, no. 5489, pp. 97–100, 2000. View at Publisher · View at Google Scholar · View at Scopus
  110. A. S. McWilliam, S. Napoli, A. M. Marsh et al., “Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli,” Journal of Experimental Medicine, vol. 184, no. 6, pp. 2429–2432, 1996. View at Publisher · View at Google Scholar · View at Scopus
  111. J. Banchereau and R. M. Steinman, “Dendritic cells and the control of immunity,” Nature, vol. 392, no. 6673, pp. 245–252, 1998. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Iwasaki and B. L. Kelsall, “Freshly isolated peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells,” Journal of Experimental Medicine, vol. 190, no. 2, pp. 229–239, 1999. View at Publisher · View at Google Scholar · View at Scopus
  113. A. Iwasaki and B. L. Kelsall, “Mucosal immunity and inflammation I. Mucosal dendritic cells: their specialized role in initiating T cell responses,” American Journal of Physiology, vol. 276, no. 5, pp. G1074–G1078, 1999. View at Google Scholar · View at Scopus
  114. I. Nukaya, M. Yasumoto, T. Iwasaki et al., “Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte,” International Journal of Cancer, vol. 80, no. 1, pp. 92–97, 1999. View at Publisher · View at Google Scholar · View at Scopus
  115. A. Porgador, H. F. Staats, Y. Itoh, and B. L. Kelsall, “Intranasal immunization with cytotoxic T-lymphocyte epitope peptide and mucosal adjuvant cholera toxin: selective augmentation of peptide-presenting dendritic cells in nasal mucosa-associated lymphoid tissue,” Infection and Immunity, vol. 66, no. 12, pp. 5876–5881, 1998. View at Google Scholar · View at Scopus
  116. J. E. Knickelbein, K. M. Khanna, M. B. Yee, C. J. Baty, P. R. Kinchington, and R. L. Hendricks, “Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency,” Science, vol. 322, no. 5899, pp. 268–271, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. K. Prabhakaran, B. S. Sheridan, P. R. Kinchington et al., “Sensory neurons regulate the effector functions of CD8+ T cells in controlling HSV-1 latency ex vivo,” Immunity, vol. 23, no. 5, pp. 515–525, 2005. View at Publisher · View at Google Scholar · View at Scopus
  118. K. M. Khanna, A. J. Lepisto, and R. L. Hendricks, “Immunity to latent viral infection: many skirmishes but few fatalities,” Trends in Immunology, vol. 25, no. 5, pp. 230–234, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. A. L. Van Lint, L. Kleinert, S. R. M. Clarke, A. Stock, W. R. Heath, and F. R. Carbone, “Latent infection with herpes simplex virus is associated with ongoing CD8+ T-cell stimulation by parenchymal cells within sensory ganglia,” Journal of Virology, vol. 79, no. 23, pp. 14843–14851, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. K. M. Khanna, R. H. Bonneau, P. R. Kinchington, and R. L. Hendricks, “Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia,” Immunity, vol. 18, no. 5, pp. 593–603, 2003. View at Publisher · View at Google Scholar · View at Scopus
  121. V. Decman, P. R. Kinchington, S. A. K. Harvey, and R. L. Hendricks, “Gamma interferon can block herpes simplex virus type 1 reactivation from latency, even in the presence of late gene expression,” Journal of Virology, vol. 79, no. 16, pp. 10339–10347, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. D. Theil, T. Derfuss, I. Paripovic et al., “Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response,” American Journal of Pathology, vol. 163, no. 6, pp. 2179–2184, 2003. View at Google Scholar · View at Scopus
  123. E. A. Kurt-Jones, M. Chan, S. Zhou et al., “Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 5, pp. 1315–1320, 2004. View at Publisher · View at Google Scholar · View at Scopus
  124. S. Zhou, E. A. Kurt-Jones, L. Mandell et al., “MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection,” European Journal of Immunology, vol. 35, no. 3, pp. 822–830, 2005. View at Publisher · View at Google Scholar · View at Scopus
  125. H. Blank and H. G. Haines, “Experimental human reinfection with herpes simplex virus,” Journal of Investigative Dermatology, vol. 61, no. 4, pp. 223–225, 1973. View at Google Scholar · View at Scopus
  126. M. P. Lazar, “Vaccination for recurrent herpes simplex infection: initiation of a new disease site following the use of unmodified material containing live virus,” Archives of Dermatology and Syphilology, vol. 73, pp. 70–71, 1956. View at Google Scholar
  127. B. Meignier, R. Longnecker, and B. Roizman, “In vivo behavior of genetically engineered herpes simplex viruses R7017 and R7020: construction and evaluation in rodents,” Journal of Infectious Diseases, vol. 158, no. 3, pp. 602–614, 1988. View at Google Scholar · View at Scopus
  128. R. J. Whitley, “Prospects for vaccination against herpes simplex virus,” Pediatric Annals, vol. 22, no. 12, pp. 726–732, 1993. View at Google Scholar · View at Scopus
  129. P. Schmersahl and G. Ruediger, “Therapeutic results with the herpes simplex antigens Lupidon H and Lupidon G,” Zeitschrift fur Hautkrankheiten, vol. 50, no. 3, pp. 105–112, 1975. View at Google Scholar
  130. A. Mastrolorenzo, L. Tiradritti, L. Salimbeni, and G. Zuccati, “Multicentre clinical trial with herpes simplex virus vaccine in recurrent herpes infection,” International Journal of STD and AIDS, vol. 6, no. 6, pp. 431–435, 1995. View at Google Scholar · View at Scopus
  131. H. Weitgasser, “Controlled clinical trial of the proprietary herpes antigens LUPIDON H and LUPIDON G,” Zeitschrift fur Hautkrankheiten, vol. 52, no. 11, pp. 625–628, 1977. View at Google Scholar · View at Scopus
  132. A. B. Kern and B. L. Schiff, “Vaccine therapy in recurrent herpes simplex,” Archives of dermatology, vol. 89, pp. 844–845, 1964. View at Google Scholar · View at Scopus
  133. G. R.B. Skinner, C. B.J. Woodman, and C. E. Hartley, “Preparation and immunogenicity of vaccine Ac NFU1 (S-) MRC towards the prevention of herpes genitalis,” British Journal of Venereal Diseases, vol. 58, no. 6, pp. 381–386, 1982. View at Google Scholar
  134. S. E. Straus, L. Corey, R. L. Burke et al., “Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes,” The Lancet, vol. 343, no. 8911, pp. 1460–1463, 1994. View at Publisher · View at Google Scholar · View at Scopus
  135. A. Forrester, H. Farrell, G. Wilkinson, J. Kaye, N. Davis-Poynter, and T. Minson, “Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted,” Journal of Virology, vol. 66, no. 1, pp. 341–348, 1992. View at Google Scholar · View at Scopus