Therapeutic Immunization for Recurrent Herpes Simplex Virus Infections

  • Robin McKenzie
  • Stephen E. Straus
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 394)


Two centuries ago Jenner dramatically demonstrated the power of vaccines for disease prevention. He protected individuals from the deadly smallpox virus by injecting them with vesicular fluid from cowpox lesions. Currently, vaccines are used world-wide as primary tools for preventing infectious diseases. In addition to this traditional role, some investigators today think vaccines can be used to treat diseases. Other scientists disagree.1 Skeptics argue that vaccines cannot boost the immune response better than the natural infection itself In the case of recurrent herpes simplex virus (HSV) infections, the virus reactivates periodically in spite of natural immunity. To be useful therapeutically, then, a vaccine would have to present herpes antigens to the immune system in a different, more effective way than they are presented by natural recurrences. Data emerging from vaccine therapy of patients with recurrent HSV infections suggests that vaccines can be used to treat disease.


Herpes Simplex Virus Type Genital Herpes Recurrent Genital Herpes Herpes Simplex Virus Glycoprotein Vesicular Fluid 
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  1. 1.
    Cohen, J. Vaccines get a new twist. Science 1994; 264: 503–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Burke RL. Current status of HSV vaccine development. In: The Human Herpesviruses. B Roizman, RJ Whitley, C Lopez (ed s). Raven Press, New York, 1993.Google Scholar
  3. 3.
    Mertz GJ, Schmidt O. Jourden JL, el al. Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts. Sex Trans Dis. 1985; 12: 3339.Google Scholar
  4. 4.
    Crocn KD, Ostrow JM, Dragovic U. Smialek JE, Straus SE. Latent herpes simplex virus in human trigeminal ganglia. N Engl J Med 1987; 314: 1427–1432.Google Scholar
  5. 5.
    Fitzgerald PA, Lopez C. Natural killer cells as mediators of resistance to herpesvirus infections in humans. In: Human Herpesvirus Infections. C Lopez. B Roizman (eds). Raven Press, New York, 1986.Google Scholar
  6. 6.
    Mester JC, Glorioso JC, Rouse BT. Protection against zosteriform spread of herpes simplex virus by monoclonal antibodies. J Infect Dis 1991; 163263–269.Google Scholar
  7. 7.
    Kohl S, Strynadka NCJ, Hodges RS, Pereira L. Analysis of the role of antibody-dependent cellular cytotoxic antibody activity in murine neonatal herpes simplex virus infection with antibodies to synthetic peptides of glycoprotein D and monoclonal antibodies to glycoprotein B. J Clin Invest 1990; 86: 273–278.PubMedCrossRefGoogle Scholar
  8. 8.
    Kohl S. Role of antibody-dependent cellular cvtotoxicity in defense against herpes simplex virus infections. Rev Infect Dis1991; 13: 108–14.Google Scholar
  9. 9.
    Rouse BJ, Norley S, Martin S. Antiviral cytotoxic T lymphocyte induction and vaccination. Rev Infect Dis 1988; 10: 16.PubMedCrossRefGoogle Scholar
  10. 10.
    Nash AA, Phelan J, Wildy P. Cell mediated immunity in herpes simplex virus infected mice: H-2 mapping of the delayed type hypersensitivity response and the antiviral T cell response. J Immunol 1981; 126: 1260.PubMedGoogle Scholar
  11. 11.
    Evans CA, Stavin HB, Berry GP. Studies on herpetic infections in mice. IV. The effect of specific antibodies on the progression of the virus within the nervous system of young mice. J Exp Med 1946; 84: 429–447.PubMedCrossRefGoogle Scholar
  12. 12.
    Cheever FS, Daikos G. Studies on the protective effect of gamma globulin against herpes simplex infections in mice. J Immunol 1950 65: 135–141.PubMedGoogle Scholar
  13. 11.
    Luyet F, Samra D, Soneji A, Marks MI. Passive immunization in experimental herpesvirus hominis infection of newborn mice. Infect Immun 1975; 12: 1258.PubMedGoogle Scholar
  14. 14.
    Simmons A, Nash AA. Role of antibody in primary and recurrent herpes simplex virus infection. J Virol 1985; 53: 944–948.PubMedGoogle Scholar
  15. 15.
    Oakes JE, Lausch RN. Monoclonal antibodies suppress replication of herpes simplex virus type 1 in trigeminal ganglia. J Virol 1984; 51: 656.PubMedGoogle Scholar
  16. 16.
    McDermott MR, Brais LJ, Evelegh MJ. Mucosal and systemic antiviral antibodies in mice inoculated intravaginally with herpes simplex virus type 2. J Gen Virol 1990; 71: 1497–1504.PubMedCrossRefGoogle Scholar
  17. 17.
    Balachandran N, Bacchetti S, Rawls WE. Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2. Infect Immun 1987; 37: 1132–1137.Google Scholar
  18. 18.
    Rector JT, Lausch RN, Oakes JE. Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection. Infect Immun 1982; 38: 168–174.PubMedGoogle Scholar
  19. 19.
    Hirsch MS, Zisman B, Allison AC. Macrophages and age-dependent resistance to herpes simplex virus in mice. J Immunol 1970; 104: 1160–1165.PubMedGoogle Scholar
  20. 20.
    Ennis FA, Wells M. Immune control of herpes simplex virus infections. Cancer Res 1974; 34: 1140 1146.Google Scholar
  21. 21.
    Nash AA, Phelan J, Wildy P. Cell-mediated immunity in herpes simplex virus-infected mice: H-2 mapping of the delayed-type hypersensitivity response and the antiviral T cell response. J Immunol 1981; 126: 1260–1262.PubMedGoogle Scholar
  22. 22.
    Igietseme JU, Streilein JW, Miranda F, Feinerman SJ, Atherton SS. Mechanisms of protection against herpes simplex virus type 1-induced retinal necrosis by in vitro-activated T lymphocytes. J Virol 1991; 65: 763–768.PubMedGoogle Scholar
  23. 23.
    Kohl S. Protection against murine neonatal herpes simplex virus infection by lymphokine-treated human leukocytes. J Immunol 1990; 144: 307–312.PubMedGoogle Scholar
  24. 24.
    Cunningham AL, Merigan TC. interferon-a production appears to predict time of recurrence of herpes labialis. J Immunol 1983; 130: 2397.Google Scholar
  25. 25.
    Hanada N, Kido S, Kuzushima K, et al. Combined effects of acyclovir and human interferon-alpha on herpes simplex virus replication in cultured neural cells. J Med Virol 1989; 29: 7–12.PubMedCrossRefGoogle Scholar
  26. 26.
    Naito T, Shiota H, Nitta K, Mimura Y. Effects on herpes simplex virus type 1 of combined use of interferon-ß and anti-herpetic agents in vitro. Jpn J Ophthalmol 1990; 34: 15–21.PubMedGoogle Scholar
  27. 27.
    Manservigi R, Incorvaia C, Di Luca D, et al. Experimental keratitis in rabbits by human HSV-1 variants: prevention and treatment. J Med Virol 1990; 32: 148–154.PubMedCrossRefGoogle Scholar
  28. 28.
    Olsen GA, Kern ER, Overall JC Jr, Glasgow LA. Effect of treatment with exogenous interferon, polyriboinosinic-polyribocytidylic acid, or polyriboinosinic-polyribocytidylic acid-poly-L-lysine complex on herpesvirus hominis infections in mice. J Infect Dis 1978; 137: 428–436.PubMedCrossRefGoogle Scholar
  29. 29.
    Pazin GJ, Armstrong JA, Lam MT, Tarr GC, Janetta PJ, Ho M. Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root. N Engl J Med 1979; 301: 225–230.PubMedCrossRefGoogle Scholar
  30. 30.
    Havenkos HW, Pagin GJ, Armstrong JA, Ho M. Follow-up of interferon treatment of/herpes simplex (letter). N Engl J Med 1980; 303: 699–700.CrossRefGoogle Scholar
  31. 31.
    Cheeseman SH, Rubin RH, Stewart JA, et al. Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation: effects on cytomegalovirus and herpes simplex virus infections. N Engl J Med 1979; 300: 1345–1349.PubMedCrossRefGoogle Scholar
  32. 32.
    Pazin GJ, Harger JH, Armstrong JA, et al. Leukocyte interferon for treating first episodes of genital herpes in women. J Infect Dis 1987; 156: 891–898.PubMedCrossRefGoogle Scholar
  33. 33.
    Kuhls TL, Sacher J, Pineda E, Santomauro D, Wiesmeier E, Growdon WA, Bryson YJ. Suppression of recurrent genital herpes simplex virus infection with recombinant alpha2 interferon. J Infect Dis 1986: 154: 437–442.PubMedCrossRefGoogle Scholar
  34. 34.
    Mendelson J, Clecner B, Eiley S. Effect of recombinant interferon alpha2 on clinical course of first episode genital herpes infection and subsequent recurrences. Genitourin Med 1986; 62: 97–101.PubMedGoogle Scholar
  35. 35.
    Levin MJ. Judson FN, Eron L. Bryson YJ, Corey L, Murray M, Scheer RR. Comparison of recombinant leukocyte interferon-alpha (rIFN-2A) with topical acyclovir for the treatment of first episode herpes genitalis and prevention of subsequent recurrences. Antimicrob Agent Chemother 1989; 33: 649–652.CrossRefGoogle Scholar
  36. 36.
    Weinberg A, Rasmussen L, Merigan TC. Acute genital infection in guinea pigs: Effect of recombinant interleukin-2 on herpes simplex virus type-2. J Infect Dis 1986; 154: 134–140.PubMedCrossRefGoogle Scholar
  37. 37.
    Weinberg A, Konrad M, Merigan TC. Regulation by recombinant interleukin-2 of protective immunity against recurrent herpes simplex virus type 2 genital infection in guinea pigs. J Virol 1987; 61: 2120 2127.Google Scholar
  38. 38.
    Weinberg A, Merigan TC. Recombinant interleukin 2 as an adjuvant for vaccine-induced protection: Immunization of guinea pigs with herpes simplex virus subunit vaccines. J Immunol 1988; 140: 294–299.PubMedGoogle Scholar
  39. 39.
    Hazama M, Mayumi-Aono A, Asakawa N, Kuroda S, Hinuma S, Fujisawa Y. Adjuvant-independent enhanced immune responses to recombinant herpes simplex virus type 1 glycoprotein D by fusion with biologically active interleukin-2. Vaccine 1993; 11: 629–636.PubMedCrossRefGoogle Scholar
  40. 40.
    Hazama M, Mayumi-Aono A, Miyazaki T, Hinuma S, Fujisawa Y. Intranasal immunization against herpes simplex virus infection by using a recombinant glycoprotein D fused with immunomodulating proteins, the B subunit of Escherichia coli heat-labile enterotoxin and interleukin-2. Immunology 1993; 78: 643–49.PubMedGoogle Scholar
  41. 41.
    Allen EM, Weir JP, Martin S, Mercadal C, Rouse BT. Role of coexpression of IL-2 and herpes simplex virus proteins in recombinant vaccinia virus vectors on levels of induced immunity. Vir Immunol 1990; 3: 207.CrossRefGoogle Scholar
  42. 42.
    Rossol-Voth R, Rossol S, Schutt KH, Corridori S, de Cian W, Falke D. In vivo protective effect of tumour necrosis factor alpha against experimental infection with herpes simplex virus type 1. J Gen Virol 1991; 72: 143–147.PubMedCrossRefGoogle Scholar
  43. 43.
    Ho RJY, Chong KT, Merigan TC. Antiviral activity and dose optimum of recombinant macrophage colony-stimulating factor on herpes simplex genitalis in guinea pigs. J Immunol 1991; 146: 3578–3582.PubMedGoogle Scholar
  44. 44.
    Douglas JM, Vontver A, Stamm WM, et al. Ineffectiveness and toxicity of BCG vaccine for the prevention of recurrent genital herpes. Antimicrob Agents Chemother 1985; 27: 203.PubMedCrossRefGoogle Scholar
  45. 45.
    Lazar MP. Vaccination for recurrent herpes simplex infection: Initiation of a new disease site following the use of unmodified material containing the live virus. Arch Dermatol 1956; 73: 70–71.CrossRefGoogle Scholar
  46. 46.
    Blank H, Haines HG. Experimental human reinfection with herpes simplex virus. J Invest Dermatol 1973; 61: 223–225.PubMedCrossRefGoogle Scholar
  47. 47.
    Meignier B, Longnecker R, Roizman B. Construction and in vivo evaluation of two genetically engineered prototypes of live attenuated herpes simples virus vaccines. In Vaccines 87. Chanock RM (ed). Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. 1987; pp. 368–373.Google Scholar
  48. 48.
    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; 158: 602–614.PubMedCrossRefGoogle Scholar
  49. 49.
    Meignier B, Martin B, Whitley RJ. Roizman B. In vivo behavior of genetically engineered herpes simplex viruses 7017 and R7020. II. Studies in immunocompetent and immunosuppressed owl monkeys (Aotus trivirgatus). J Infect Dis 1990; 162: 313–321.PubMedCrossRefGoogle Scholar
  50. 50.
    Cadoz M, Micoud M, Seigneurin JM, et al. Phase 1 trial of R7020: a live attenuated recombinant herpes simplex virus (HSV) candidate vaccine. (Abstract #341) 32nd ICAAC, Anaheim, CA, 1992.Google Scholar
  51. 51.
    Whitley RI. Prospects for vaccination against herpes simplex virus. Ped Ann 1993; 22: 726–732.Google Scholar
  52. 52.
    Whitley RJ, Kern ER, Chatterjee S, Chou J, Roizman B. Replication, establishment of latency, and induced reactivation of herpes simplex virus 34.5 deletion mutants in rodent models. J Clin Invest 1993; 91: 2837–2843.PubMedCrossRefGoogle Scholar
  53. 53.
    Forrester A, Farrell H, Wilkinson G, et al. Construction and properties of a mutant herpes simplex virus type 1 with glycoprotein gH sequences deleted. J Virol 1992; 66:34 l-348.Google Scholar
  54. 54.
    McLean CS, Erturk M, Jennings R, et al. 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: 170: 1100–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Wachsman M, Aurelian L. Smith CC. Lipinskas BR. Perkus ME, Paoletti E. Protection of guinea pigs from primary and recurrent herpes simplex virus (HSV) type 2 cutaneous disease with vaccinia virus recombinants expressing HSV glycoprotein D. J Infect Dis 1987; 155:1188–1197_Google Scholar
  56. 56.
    Cremer KJ, Mackett M, Wohlenberg C. Norkins AL, Moss B. Vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D prevents latent herpes in mice. Science 1985: 228: 737–740.PubMedCrossRefGoogle Scholar
  57. 57.
    Rooney JF, Wohlenberg C. Cremer KJ. Norkins AL. Immunized mice challenged with herpes simplex virus by the intranasal route show protection against latent infection. J Infect Dis 1989; 159: 974–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Wachsman M. Aurelian L, Smith CC, Perkus ME, Paoletti E. Regulation of expression of herpes simplex virus (HSV) glycoprotein D in vaccinia recombinants affects their ability to protect from cutaneous HSV2 disease. J Infect Dis 1989: 159: 625–634.PubMedCrossRefGoogle Scholar
  59. 59.
    Rooney JF, Wohlenberg C, Cremer KJ, Moss B, Notkins AL. Immunization with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and effect of revaccination. J Virol 1988; 62: 1530–1534.PubMedGoogle Scholar
  60. 60.
    McDermott MR, Graham FL, Hanke T, Johnson DC. Protection of mice against lethal challenge with herpes simplex virus by vaccination with an adenovirus vector expressing HSV glycoprotein B. Virology 1989; 169: 244–247.PubMedCrossRefGoogle Scholar
  61. 61.
    Gallichan WS, Johnson DC, Graham FL, Rosenthal KL. Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B. J Infect Dis 1993; 168: 622–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Dix RD. Prospects for a vaccine against herpes simplex virus types 1 and 2. Prog Med Virol 1987; 34: 89–128.PubMedGoogle Scholar
  63. 63.
    Stanberry LR. Subunit viral vaccines: prophylactic and therapeutic use. In: Herpesviruses, the Immune System, and AIDS. Aurelian L (ed). Kluwer Academic Press, Norwell, MA, pp 309–341, 1990.Google Scholar
  64. 64.
    Kern AB, Schiff BL. Vaccine therapy in recurrent herpes simplex. Dermatology 1964; 89: 844–845.CrossRefGoogle Scholar
  65. 65.
    Schmersahl P, Rudiger G. Behandlungsergebnisse mit dem Herpes simplex-Antigen Lupidon H bzw. Lupidon G. Z Hautarzt 1975; 50: 105.Google Scholar
  66. 66.
    Dundarov S, Andonov P, Bakalov B, Nechev K, Tomov C. Immunotherapy with inactivated polyvalent herpes vaccines. Dev Biol Stan 1982; 52: 351–358.Google Scholar
  67. 67.
    Weitgasser H. Kontrollierte klinische Studie mit den Herpes-Antigenen Lupidon H und Lupidon G. Z Hautkr 1977; 52: 624–628.Google Scholar
  68. 68.
    Skinner GRB, Fink CG, Durham J, et al. Follow-up report on 101 subjects vaccinated with Skinner herpes vaccine. In: Vaccines for Sexually Transmitted Diseases. Meheus A, Spier RE (eds). Butterworths, London, pp 202–207, 1989.Google Scholar
  69. 69.
    Skinner GRB, Woodman CBJ, Hartley CE, et al. Early experience with “antigenoid” vaccine Ac Nful, (S-) MRC towards prevention or modification of herpes genitalis. Dev Biol Stan 1982; 52: 333–344.Google Scholar
  70. 70.
    Woodman CBJ, Buchan A, Fuller A, et al. Efficacy of vaccine Ac Nfui, (S-) MRC given after an initial clinical episode in the prevention of herpes genitalis. Br J Vener Dis 1983; 59: 311–313.PubMedGoogle Scholar
  71. 71.
    Cappel R, Sprecher S, DeCuyper F, DeBraekeleer J. Clinical efficacy of a herpes simplex subunit vaccine. J Med Virol 1985; 16: 137–145.PubMedCrossRefGoogle Scholar
  72. 72.
    Kutinovâ L, Benda R, Kalos Z, et al. Placebo-controlled study with subunit herpes simplex virus vaccine in subjects suffering from frequent herpetic recurrences. Vaccine 1988; 6: 223–228.PubMedCrossRefGoogle Scholar
  73. 73.
    Mertz GJ, Ashley R, Burke RL, Benedetti J, Critchlow C, Jones CC, Corey L. Double-blind, placebo-controlled trial of a herpes simplex virus type-2 glycoprotein vaccine in persons at high risk for genital herpes infection. J Infect Dis 1990; 161: 653–660.PubMedCrossRefGoogle Scholar
  74. 74.
    Frenkel LM, Dillon M, Garraty E, et al. A randomized double blind, placebo-controlled phase 1 trial of a herpes simplex virus purified glycoprotein (gDl) vaccine. (Abstract #506), 30th Interscience Conference on Antibimocrobial Agents and Chemotherapy, Atlanta, Ga, 1990.Google Scholar
  75. 75.
    Morein B, Simons K. Subunit vaccines against enveloped viruses: virosomes, micelles and other protein complexes. Vaccine 1985; 3: 83–93.PubMedCrossRefGoogle Scholar
  76. 76.
    Ho RJY, Burke RL, Merigan TC. Antigen-presenting liposomes are effective in treatment of recurrent herpes simplex virus genitalis in guinea pigs. J Virol 1989; 63: 2951–2958.PubMedGoogle Scholar
  77. 77.
    Sanchez-Pescador L, Burke RL, Ott G, Van Nest G. The effect of adjuvants on the efficacy of a recombinant herpes simplex virus glycoprotein vaccine. J Immunol 1988; 141: 1720–1727.PubMedGoogle Scholar
  78. 78.
    Burke RL, Goldbeck C, Ng P, Stanberry L, Ott G, Van Nest G. The influence of adjuvant on the therapeutic efficacy of a recombinant genital herpes vaccine. J Infect Dis 1994; 170: 1110–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Berman PW, Gregory T, Crase D, Lasky LA. Protection from genital herpes simplex virus type 2 infection by vaccination with cloned type 1 glycoprotein D. Science 1985; 227: 1490–1492.PubMedCrossRefGoogle Scholar
  80. 80.
    Stanberry LR, Bernstein DI, Burke RL, Pachl C, Myers MG. Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes. J Infect Dis 1987; 155: 914–920.PubMedCrossRefGoogle Scholar
  81. 81.
    Burke RL, Hartog K, Croen KD, Ostrove JM. Detection and characterization of latent HSV RNA by in situ and Northern Blot hybridization in guinea pigs. Virology 1991; 181: 793–797.PubMedCrossRefGoogle Scholar
  82. 82.
    Stanberry LR, BUrke RL, Myers MG. Herpes simplex virus glycoprotein treatment of recurrent genital herpes. J Infect Dis 1988; 157: 156–163.PubMedCrossRefGoogle Scholar
  83. 83.
    Stanberry LR, Harrison CJ, Bernstein DI, BUrke RL, Shukla R, Ott G. Myers MG. Herpes simplex virus glycoprotein immunotherapy of recurrent genital herpes: factors influencing efficacy. Antiviral Res 1989; 11: 203–214.PubMedCrossRefGoogle Scholar
  84. 84.
    Eisenberg RJ, Cerini CP, Heilman CJ, et al. Synthetic glycoprotein D-related peptides protect mice against herpes simplex virus challenge. J Virol 1985; 56: 1014–1017.PubMedGoogle Scholar
  85. 85.
    Geerligs HJ, Kocken CHM, Drijfhout JW, et al. Virus neutralizing activity induced by synthetic peptides of glycoprotein D of herpes simplex virus type 1, selected by their reactivity with hyperimmune sera from mice. J Gen Virol 1990; 71: 1767–1774.PubMedCrossRefGoogle Scholar
  86. 86.
    Straus SE, Savarese B, Tigges M,et al. Induction and enhancement of immune responses to herpes simplex virus type 2 in humans by use of a recombinant glycoprotein D vaccine. J Infect Dis 1993; 167: 1045–52.PubMedCrossRefGoogle Scholar
  87. 87.
    Straus SE, Corey L, Burke RL, et al. Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet 1994; 343: 1460–3.PubMedCrossRefGoogle Scholar
  88. 88.
    Langenberg AGM, Sekulovich R, Douglas J, et al. Addition of recombinant HSV-2 gB to a gD2 vaccine improves the kinetics, magnitude and durability of antibody responses in humans. (Abstract #H7) 34th ICAAC, Orlando, FL, 1994.Google Scholar
  89. 89.
    Leroux-Roels G, Moreau E, Verhasselt B, et al. Immunogenicity and reactogenicity of a recombinant HSV-2 glycoprotein D vaccine with or without mono-phosphoryl lipid A in HSV seronegative and seropositive subjects. (Abstract #1209) 33rd ICAAC, New Orleans, LA,1993.Google Scholar
  90. 90.
    Leroux-Roels G, Moreau E, Desombere I, et al. Persistence of humoral and cellular immune response and booster effect following vaccination with herpes simplex (gD2t) candidate vaccine with MPL. (Abstract #H57) 34th ICAAC, Orlando, Fl, 1994.Google Scholar
  91. 91.
    Committee on Issues and Priorities for New Vaccine Development. In: New Vaccine Development: Establishing Priorities. National Academy Press, Washington, DC, pp 280–312, 1985.Google Scholar

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© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Robin McKenzie
  • Stephen E. Straus

There are no affiliations available

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