Vaccine Strategies for the Prevention of Cytomegalovirus Disease

  • Gary S. Marshall
  • Stanley A. Plotkin
Part of the Frontiers of Virology book series (FRVIROLOGY, volume 2)


The theorectical basis for vaccine immunoprophylaxis against cytomegalovirus rests on observations that naturally immune hosts are protected from disease, even though they may not be protected from infection per se. Indirect support for the vaccine paradigm derives from experimental models in the mouse and guinea pig, although these models are imperfect since they necessarily involve infection with species-specific cytomegaloviruses. Direct evidence is now available with the completion of a randomized, double-blind, placebo-controlled trial of Towne strain live attenuated vaccine in renal transplant patients. In seronegative patients who received kidneys from seropositive donors, the vaccine was able to prevent severe disease, albeit not infection; this is analogous to the protection afforded by natural immunity. Because theoretical safety concerns about a live herpesvirus vaccine exist, there is interest in developing noninfectious subunits that would mimic or exceed the immunogenicity of live whole virus. The abundant envelope glycoprotein gB is currently the most promising candidate, but other subunits, including immediate early proteins and other surface glycoproteins, are being investigated. Future work will concentrate on further study of the protective immune response to natural infection, testing live vaccines in other susceptible populations, and developing optimal vectors for the delivery of immunogenic subunits.


Human Cytomegalovirus Cytomegalovirus Infection Immediate Early Murine Cytomegalovirus Cytomegalovirus Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Yow MD (1989) Congenital cytomegalovirus disease: a NOW problem. J Infect Dis 159: 163–167PubMedGoogle Scholar
  2. 2.
    Jacobson MA, Mills J (1988) Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS): clinical findings, diagnosis and treatment. Ann Intern Med 180: 585–594Google Scholar
  3. 3.
    Glenn J (1981) Cytomegalovirus infections following renal transplantation. Rev Infect Dis 3: 1154–1178Google Scholar
  4. 4.
    Meyers JD (1984) Cytomegalovirus infection following marrow transplantation: risk, treatment, and prevention. Birth Defects 20: 101–117PubMedGoogle Scholar
  5. 5.
    Davis CL (1990) The prevention of cytomegalovirus disease in renal transplantation. Am J Kidney Dis 16: 175–188PubMedGoogle Scholar
  6. 6.
    Editorial (1989) Screening for congenital CMV. Lancet 2: 599–600Google Scholar
  7. 7.
    Alford CA, Stagno S, Pass RF, Britt WJ (1990) Congenital and perinatal cytomegalovirus infections. Rev Infect Dis 12: 5745 — S753Google Scholar
  8. 8.
    Ahlfors K, Harris S, Ivarsson S, Svanberg L (1981) Secondary maternal cytomegalovirus infection causing symtomatic congenital infection. N Engl J Med 305: 284PubMedGoogle Scholar
  9. 9.
    Rutter D, Griffiths P, Trompeter RS (1985) Cytomegalic inclusion disease after recurrent maternal infection. Lancet 2: 1182PubMedGoogle Scholar
  10. 10.
    Stagno S, Pass RF, Dworsky ME et al. (1982) Congenital cytomegalovirus infection: the relative importance of primary and recurrent maternal infection. N Engl J Med 306: 945–949PubMedGoogle Scholar
  11. 11.
    Stagno S, Pass RF, Cloud G et al. (1986) Primary cytomegalovirus infection in pregnancy: incidence, transmission to fetus, and clinical outcome. JAMA 256: 1904–1908PubMedGoogle Scholar
  12. 12.
    Pass RF, Little EA, Stagno S et al. (1987) Young children as a probable source of maternal and congenital infection. N Engl J Med 316: 1366–1370PubMedGoogle Scholar
  13. 13.
    White NH, Yow MD, Demmler GJ et al. (1989) Prevalence of cytomegalovirus antibody in subjects between the ages of 6 and 22 years. J Infect Dis 159: 1013–1017PubMedGoogle Scholar
  14. 14.
    Bart KJ, Orenstein WA, Preblud SR, Hinman AR (1985) Universal immunization to interrupt rubella. Rev Infect Dis 7: S177 — S184PubMedGoogle Scholar
  15. 15.
    Chou S (1986) Acquisition of donor strains of cytomegalovirus by renal-transplant recipients. N Engl J Med 314: 1418–1423PubMedGoogle Scholar
  16. 16.
    Chandler SH, Handsfield HH, McDougall JK (1987) Isolation of multiple strains of cytomegalovirus from women attending a clinic for sexually transmitted diseases. J Infect Dis 155: 655–660PubMedGoogle Scholar
  17. 17.
    Chou S (1987) Cytomegalovirus infection and reinfection transmitted by heart transplantation. J Infect Dis 155: 1054–1056PubMedGoogle Scholar
  18. 18.
    Grundy JE, Lui SF, Super M et al. (1988) Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. Lancet 2: 132–135PubMedGoogle Scholar
  19. 19.
    Collier AC, Chandler SH, Handsfield HH et al. (1989) Identification of multiple strains of cytomegalovirus in homosexual men. J Infect Dis 159: 123–126PubMedGoogle Scholar
  20. 20.
    Plotkin SA, Starr SE, Friedman HM et al. (1989) Protective effects of Towne cytomegalovirus vaccine against low-passage cytomegalovirus administered as a challenge. J Infect Dis 159: 860–865PubMedGoogle Scholar
  21. 21.
    Ho M (1984) Immunology of cytomegalovirus Immunosuppressive effects during infections. Birth Defects 20: 131–147PubMedGoogle Scholar
  22. 22.
    Rook AH (1988) Interactions of cytomegalovirus with the human immune system. Rev Infect Dis 10: 5460–5467Google Scholar
  23. 23.
    Starr SE, Dalton B, Garrabrant T et al. (1980) Lymphocyte blastogenesis and interferon production in adult human leukocyte cultures stimulated with cytomegalovirus antigens. Infect Immun 30: 17–22PubMedGoogle Scholar
  24. 24.
    Quinnan GV, Burns WH, Kirmani N et al. (1984) HLA-restricted cytotoxic T lymphocytes are an early immune response and important defense mechanism in cytomegalovirus infections. Rev Infect Dis 6: 156–163PubMedGoogle Scholar
  25. 25.
    Rinaldo CR Jr, Ho M, Hamoudi WH et al. (1983) Lymphocyte subsets and natural killer cell responses during cytomegalovirus mononucleosis. Infect Immun 40: 472–477PubMedGoogle Scholar
  26. 26.
    Osborn JE (1981) Cytomegalovirus: pathogenicity, immunology, and vaccine initiatives. J Infect Dis 143: 618–630PubMedGoogle Scholar
  27. 27.
    Middledorp JM, Jongsma J, The TH (1986) Killing of human cytomegalovirus-infected fibroblasts by antiviral antibody and complement. J Infect Dis 153: 48–55Google Scholar
  28. 28.
    Shanley JD, Jordan MC, Stevens JG (1981) Modification by adoptive humoral immunity of murine cytomegalovirus infection. J Infect Dis 143: 231–237PubMedGoogle Scholar
  29. 29.
    Snydman DR, Werner BG, Heinze-Lacey B et al. (1987) Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med 317: 1049–1054PubMedGoogle Scholar
  30. 30.
    Yeager AS, Grumet FC, Hafleigh EG et al. (1981) Prevention of transfusion-acquired cytomegalovirus infections in newborn infants. J Pediatr 98: 281–287PubMedGoogle Scholar
  31. 31.
    Griffiths PD, Baboonian C (1984) A prospective study of primary cytomegalovirus infection during pregnancy: final report. Br J Obstet Gynaecol 91: 307–315PubMedGoogle Scholar
  32. 32.
    Yow MD, Williamson DW, Leeds LJ et al. (1988) Epidemiologic characteristics of cytomegalovirus infection in mothers and their infants. Am J Obstet Gynecol 158: 1189–1195PubMedGoogle Scholar
  33. 33.
    Alford CA, Hayes K, Britt W (1988) Primary cytomegalovirus infection in pregnancy: comparison of antibody responses to virus-encoded proteins between women with and without intrauterine infection. J Infect Dis 158: 917–924PubMedGoogle Scholar
  34. 34.
    Britt WJ, Vugler LG (1990) Antiviral antibody responses in mothers and their newborn infants with clinical and subclinical congenital cytomegalovirus infections. J Infect Dis 161: 214–219PubMedGoogle Scholar
  35. 35.
    Stern H, Hannington G, Booth J, Moncrieff D (1986) An early marker of fetal infection after primary cytomegalovirus infection in pregnancy. Br Med J 292: 718–720Google Scholar
  36. 36.
    Chou S (1989) Reactivation and recombination of multiple cytomegalovirus strains from individual organ donors. J Infect Dis 160: 11–15PubMedGoogle Scholar
  37. 37.
    Smiley ML, Wlodaver CG, Grossman RA et al. (1985) The role of pretransplant immunity in protection from cytomegalovirus disease following renal transplantation. Transplantation 40: 157–161PubMedGoogle Scholar
  38. 38.
    Hudson JB (1979) The murine cytomegalovirus as a model for the study of viral pathogenesis and persistent infections: brief review. Arch Virol 62: 1–29PubMedGoogle Scholar
  39. 39.
    Johnson KP (1969) Mouse cytomegalovirus: placental infection. J Infect Dis 120: 445450Google Scholar
  40. 40.
    Osborn JE, Walker DL (1970) Virulence and attenuation of murine cytomegalovirus. Infect Immun 3: 228–236Google Scholar
  41. 41.
    Minamishima Y, Eizuru Y, Yoshida A, Fukunishi R (1978) Murine model for immunoprophylaxis of cytomegalovirus infection. I. Efficacy of immunization. Microbiol Immunol 22: 693–700Google Scholar
  42. 42.
    Howard RJ, Balfour HH Jr (1977) Prevention of morbidity and mortality of wild murine cytomegalovirus by vaccination with attenuated cytomegalovirus. Proc Soc Exp Biol Med 156: 365–368PubMedGoogle Scholar
  43. 43.
    Chong KT, Mims CA (1981) Murine cytomegalovirus particle types in relation to sources of virus and pathogenicity. J Gen Virol 57: 415–419PubMedGoogle Scholar
  44. 44.
    Ravindranath RMH, Graves MC (1990) Attenuated murine cytomegalovirus binds to N-acetylglucosamine, and shift to virulence may involve recognition of sialic acids. J Virol 64:5430 —5440Google Scholar
  45. 45.
    Chantler JK, Misra V, Hudson JB (1979) Vertical transmission of murine cytomegalovirus. J Gen Virol 42: 621–625PubMedGoogle Scholar
  46. 46.
    Jordan MC (1980) Adverse effects of cytomegalovirus vaccination in mice. J Clin Invest 65: 798–803PubMedGoogle Scholar
  47. 47.
    Bia FJ, Griffith BP, Fong CKY, Hsiung GD (1983) Cytomegalovirus infections in the guinea pig. Experimental models for human disease. Rev Infect Dis 5: 177–195Google Scholar
  48. 48.
    Kumar ML, Nankervis GA (1978) Experimental congenital infection with cytomegalovirus. A guinea pig model. J Infect Dis 138: 650–654Google Scholar
  49. 49.
    Harrison CJ, Meyers MG (1990) Relation of maternal CMV viremia and antibody response to the rate of congenital infection and intrauterine growth retardation. J Med Virol 31: 222–228PubMedGoogle Scholar
  50. 50.
    Bia FJ, Griffith BP, Tarsio M, Hsiung GD (1980) Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus. J Infect Dis 142: 732–738PubMedGoogle Scholar
  51. 51.
    Bia FJ, Miller SA, Lucia HL et al. (1984) Vaccination against transplacental cytomegalovirus transmission: vaccine reactivation and efficacy in guinea pigs. J Infect Dis 149: 355–362PubMedGoogle Scholar
  52. 52.
    Elek SD, Stern H (1974) Development of a vaccine against mental retardation caused by cytomegalovirus infection in utero. Lancet 1: 1–4PubMedGoogle Scholar
  53. 53.
    Neff BJ, Weibel RE, Buynak EB et al. (1979) Clinical and laboratory studies of live cytomegalovirus vaccine AD-169. Proc Soc Exp Biol Med 160: 32–37PubMedGoogle Scholar
  54. 54.
    Stern H (1984) Live cytomegalovirus vaccination of healthy volunteers: eight-year followup studies. Birth Defects 20: 263–269PubMedGoogle Scholar
  55. 55.
    Plotkin SA, Furukawa T, Zygraich N, Huygelen C (1975) Candidate cytomegalovirus strain for human vaccination. Infect Immun 12: 521–527PubMedGoogle Scholar
  56. 56.
    Just M, Buergin-Wolff A, Emoedi G, Hernandez R (1975) Immunization trials with live attenuated cytomegalovirus Towne-125. Infection 3: 111–114PubMedGoogle Scholar
  57. 57.
    Quinnan GV, Delery M, Rook AH et al. (1984) Comparative virulence and immunogenicity of the Towne strain and a nonattenuated strain of cytomegalovirus. Ann Intern Med 101: 478–483PubMedGoogle Scholar
  58. 58.
    Plotkin SA, Farquhar J, Hornberger E (1976) Clinical trials of immunization with the Towne 125 strain of human cytomegalovirus. J Infect Dis 134: 470–475PubMedGoogle Scholar
  59. 59.
    Gehrz RC, Christianson WR, Linner KM et al. (1980) Cytomegalovirus vaccine: specific humoral and cellular immune responses in human volunteers. Arch Intern Med 140: 936–939PubMedGoogle Scholar
  60. 60.
    Sachs GW, Simmons RL, Balfour HH (1984) Cytomegalovirus vaccine: persistence of humoral immunity following immunization of renal transplant candidates. Vaccine 2: 215–218PubMedGoogle Scholar
  61. 61.
    Starr SE, Glazer JP, Friedman HM et al. (1981) Specific cellular and humoral immunity after immunization with live Towne strain cytomegalovirus vaccine. J Infect Dis 143: 585–589PubMedGoogle Scholar
  62. 62.
    Fleisher GR, Starr SE, Friedman HM, Plotkin SA (1982) Vaccination of pediatric nurses with live attenuated cytomegalovirus. Am J Dis Child 136: 294–296PubMedGoogle Scholar
  63. 63.
    Carney WP, Hirsch MS, Iacoviello VR et al. (1983) T-lymphocyte subsets and proliferative responses following immunization with cytomegalovirus vaccine. J Infect Dis 147: 958PubMedGoogle Scholar
  64. 64.
    Glazer JP, Friedman HM, Grossman RA et al. (1979) Live cytomegalovirus vaccination of renal transplant candidates. A preliminary trial. Ann Intern Med 91: 676–683PubMedGoogle Scholar
  65. 65.
    Balfour HH Jr, Welo PK, Sachs GW (1985) Cytomegalovirus vaccine trial in 400 renal transplant candidates. Transplant Proc 17: 81–83Google Scholar
  66. 66.
    Plotkin SA, Starr SE, Friedman HM et al. (1991) Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. A controlled trial. Ann Intern Med 114: 525–531PubMedGoogle Scholar
  67. 67.
    Plotkin SA, Huang E-S (1985) Cytomegalovirus vaccine virus ( Towne strain) does not induce latency. J Infect Dis 152: 395–397Google Scholar
  68. 68.
    Porath A, McNutt RA, Smiley LM, Weigle KA (1990) Effectiveness and cost benefit of a proposed live cytomegalovirus vaccine in the prevention of congenital disease. Rev Infect Dis 12: 31–40PubMedGoogle Scholar
  69. 69.
    Ada GL (1990) The immunological principles of vaccination. Lancet 1: 523–526Google Scholar
  70. 70.
    Furukawa T, Gonczol E, Starr S et al. (1984) HCMV envelope antigens induce both humoral and cellular immunity in guinea pigs. Proc Soc Exp Biol Med 175: 243–250PubMedGoogle Scholar
  71. 71.
    Balachandran N, Bacchetti S, Rawls WE (1982) 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 37: 1132–1137PubMedGoogle Scholar
  72. 72.
    Berman PW, Gregory T, Crase D, Lasky LA (1985) Protection from genital herpes simplex virus type 2 infection by vaccination with cloned type 1 glycoprotein D. Science 227: 1490–1492PubMedGoogle Scholar
  73. 73.
    Gretch DR, Kari B, Rasmussen L et al. (1988) Identification and characterization of three distinct families of glycoprotein complexes in the envelopes of human cytomegalovirus. J Virol 62: 875–881PubMedGoogle Scholar
  74. 74.
    Kari B, Lussenhop N, Goertz R et al. (1986) Characterization of monoclonal antibodies reactive to several biochemically distinct human cytomegalovirus glycoprotein complexes. J Virol 60: 345–352PubMedGoogle Scholar
  75. 75.
    Gretch DR, Kari B, Grehrz RC, Stinski MF (1988) A multigene family encodes the human cytomegalovirus glycoprotein complex gcll (gp 47–52 complex). J Virol 62:1956 —1962Google Scholar
  76. 76.
    Rasmussen LE, Nelson RM, Kelsall DC, Merigan TC (1984) Murine monoclonal antibody to a single protein neutralizes the infectivity of human cytomegalovirus. Proc Natl Acad Sci USA 81: 876–880PubMedGoogle Scholar
  77. 77.
    Rasmussen L, Mullenax J, Nelson M, Merigan TC (1985) Human cytomegalovirus polypeptides stimulate neutralizing antibody in vivo. Virology 145: 186–190PubMedGoogle Scholar
  78. 78.
    Cranage MP, Smith GL, Bell SE et al. (1988) Identification and expression of a human cytomegalovirus glycoprotein with homology to the Epstein-Barr virus BXLF2 product, varicella-zoster virus gpIII, and herpes simplex virus type 1 glycoprotein H. J Virol 62: 1416–1422PubMedGoogle Scholar
  79. 79.
    Pachl C, Probert WS, Hermsen KM et al. (1989) The human cytomegalovirus strain Towne glycoprotein H gene encodes glycoprotein p86. Virology 169: 418–426PubMedGoogle Scholar
  80. 80.
    Keay S, Baldwin B (1991) Anti-idiotype antibodies that mimic gp86 of human cytomegalovirus inhibit viral fusion but not attachment. J Virol 65: 5124–5128PubMedGoogle Scholar
  81. 81.
    Pereira L, Hoffman M, Tatsuno M, Dondero D (1984) Polymorphism of human cytomegalovirus glycoproteins characterized by monoclonal antibodies. Virology 139: 73–86PubMedGoogle Scholar
  82. 82.
    Cranage MP, Kouzarides T, Bankier AT et al. (1986) Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus. EMBO J 5: 3057–3063PubMedGoogle Scholar
  83. 83.
    Britt WJ (1984) Neutralizing antibodies detect a disulfide-linked glycoprotein complex within the envelope of human cytomegalovirus. Virology 135: 369–378PubMedGoogle Scholar
  84. 84.
    Rasmussen L, Mullenax J, Nelson R, Merigan TC (1985) Viral polypeptides detected by a complement-dependent neutralizing murine antibody to human cytomegalovirus. J Virol 55: 274–280PubMedGoogle Scholar
  85. 85.
    Gonczol E, Hudecz F, Ianocone J et al. (1986) Immune responses to isolated human cytomegalovirus envelope proteins. J Virol 58: 661–664PubMedGoogle Scholar
  86. 86.
    Britt WJ, Vugler L, Stephens EB (1988) Induction of complement-dependent and -independent neutralizing antibodies by recombinant-derived human cytomegalovirus gp55–116 (gB). J Virol 62: 3309–3318PubMedGoogle Scholar
  87. 87.
    Marshall GS, Ricciardi RP, Rando RF et al. (1990) An adenovirus recombinant that expresses the human cytomegalovirus major envelope glycoprotein and induces neutralizing antibodies. J Infect Dis 162: 1177–1181PubMedGoogle Scholar
  88. 88.
    Top FH Jr, Grossman RA, Bartelloni PJ et al. (1971) Immunization with live types 7 and 4 adenovirus vaccines. I. Safety, infectivity, and potency of adenovirus type 7 vaccine in humans. J Infect Dis 124: 148–154PubMedGoogle Scholar
  89. 89.
    Top FH Jr, Buescher EL, Bancroft WH, Russell PK (1971) Immunization with live types 7 and 4 adenovirus vaccines. II. Antibody response and protective effect against acute respiratory disease due to adenovirus type 7. J Infect Dis 124: 155–160PubMedGoogle Scholar
  90. 90.
    Spaete RR, Thayer RM, Probert WS et al. (1988) Human cytomegalovirus strain Towne glycoprotein B is processed by proteolytic cleavage. Virology 167: 207–225PubMedGoogle Scholar
  91. 91.
    Britt WJ, Auger D (1986) Synthesis and processing of the envelope gp55–116 complex of human cytomegalovirus. J Virol 58: 185–191PubMedGoogle Scholar
  92. 92.
    Britt WJ, Vugler LG (1989) Processing of the gp55–116 envelope glycoprotein complex of human cytomegalovirus. J Virol 63: 403–410PubMedGoogle Scholar
  93. 93.
    Spaete RR, Saxena A, Scott PI et al. (1990) Sequence requirements for proteolytic processing of glycoprotein B of human cytomegalovirus strain Towne. J Virol 64: 29222931Google Scholar
  94. 94.
    Lussenhop NO, Goertz R, Wabuke-Bunoti M et al. (1988) Epitope analysis of human cytomegalovirus glycoprotein complexes using murine monoclonal antibodies. Virology 164: 362–372PubMedGoogle Scholar
  95. 95.
    Utz U, Britt W, Vugler L, Mach M (1989) Identification of a neutralizing epitope on glycoprotein gp58 of human cytomegalovirus. J Virol 63: 1995–2001PubMedGoogle Scholar
  96. 96.
    Kneiss N, Mach M, Fay J, Britt WJ (1991) Distribution of linear antigenic sites on glycoprotein gp55 of human cytomegalovirus. J Virol 65: 138–146Google Scholar
  97. 97.
    Law KM, Wilton-Smith P, Farrar GH (1985) A murine monoclonal antibody recognizing a single glycoprotein within a human cytomegalovirus virion envelope glycoprotein complex. J Med Virol 17: 255–266PubMedGoogle Scholar
  98. 98.
    Farrar GH, Greenaway PJ (1986) Characterization of glycoprotein complexes present in human cytomegalovirus envelopes. J Gen Virol 67: 1469–1473PubMedGoogle Scholar
  99. 99.
    Gretch DR, Gehrz RC, Stinski MF (1988) Characterization of a human cytomegalovirus glycoprotein complex (geI). J Gen Virol 69: 1205–1215PubMedGoogle Scholar
  100. 100.
    Meyer H, Masuho Y, Mach M (1990) The gp116 of the gp58/116 complex of human cytomegalovirus represents the amino-terminal part of the precursor molecule and contains a neutralizing epitope. J Gen Virol 71: 2443–2450PubMedGoogle Scholar
  101. 101.
    Liu Y-N, Kari B, Gehrz RC (1988) Human immune responses to major human cytomegalovirus glycoprotein complexes. J Virol 62: 1066–1070PubMedGoogle Scholar
  102. 102.
    Britt WJ, Vugler L, Butfiloski EJ, Stephens EB (1990) Cell surface expression of human cytomegalovirus (HCMV) gp55–116 (gB): use of HCMV-recombinant vaccinia virus-infected cells in analysis of the human neutralizing antibody response. J Virol 64: 10791085Google Scholar
  103. 103.
    Marshall GS, Rabalais GP, Stout GG, Waldeyer SL (1992) Antibodies to recombinant-derived glycoprotein B after natural human cytomegalovirus infection correlate with neutralizing activity. J Infect Dis 165: 381–384PubMedGoogle Scholar
  104. 104.
    Gonczol E, Ianacone J, Ho W et al. (1990) Isolated gA/gB glycoprotein complex of human cytomegalovirus envelope induces humoral and cellular immune-response in human volunteers. Vaccine 8: 130–136PubMedGoogle Scholar
  105. 105.
    Landini MP, Rossier E, Schmitz H (1988) Antibodies to human cytomegalovirus structural polypeptides during primary infection. J Virol Methods 22: 309–317PubMedGoogle Scholar
  106. 106.
    Spencer ES, Andersen HK (1972) The development of immunofluorescent antibodies as compared with complement-fixing and virus neutralizing antibodies in human cytomegalovirus infection. Scand J Infect Dis 4: 109–112PubMedGoogle Scholar
  107. 107.
    Forman SJ, Zaia JA, Clark BR et al. (1985) A 64000 dalton matrix protein of human cytomegalovirus induces in vitro immune responses similar to those of whole viral antigen. J Immunol 134: 3391–3395PubMedGoogle Scholar
  108. 108.
    Landini MP, Michelson S (1988) Human cytomegalovirus proteins. Prog Med Virol 35: 152–185PubMedGoogle Scholar
  109. 109.
    Reddehase MJ, Keil GM, Koszinowski UH (1984) The cytolytic T lymphocyte response to the murine cytomegalovirus. II. Detection of virus replication stage-specific antigens by separate populations of in-vivo active cytolytic T lymphocyte precursors. Eur J Immunol 14: 56–61Google Scholar
  110. 110.
    Reddehase MJ, Koszinowski UH (1984) Significance of herpes-virus immediate early gene expression in cellular immunity to cytomegalovirus infection. Nature 312: 369–371PubMedGoogle Scholar
  111. 111.
    Koszinowski UH, Reddehase MJ, Keil GM, Schickedanz J (1987) Host immune response to cytomegalovirus. Products of transfected viral immediate-early genes are recognized by cloned cytolytic T lymphocytes. J Virol 61: 2054–2058Google Scholar
  112. 112.
    Jonjic S, del Val M, Keil GM et al. (1988) A nonstructural viral protein expressed by a recombinant vaccina virus protects against lethal cytomegalovirus infection. J Virol 62: 1653–1658PubMedGoogle Scholar
  113. 113.
    Reddehase MJ, Mutter W, Munch K et al. (1987) CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. J Virol 61: 3102–3108PubMedGoogle Scholar
  114. 114.
    Jonjic S, Pavic I, Lucin P et al. (1990) Efficacious control of cytomegalovirus infection after long-term depletion of CD8 + T lymphocytes. J Virol 64: 5457–5464PubMedGoogle Scholar
  115. 115.
    Del Val M, Volkmer H, Rothbard JB et al. (1988) Molecular basis for cytolytic T-lymphocyte recognition of the murine cytomegalovirus immediate-early protein pp89. J Virol 62: 3965–3972PubMedGoogle Scholar
  116. 116.
    Del Val M, Schlicht H-J, Volkmer H et al. (1991) Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. J Virol 65: 3641–3646PubMedGoogle Scholar
  117. 117.
    Borysiewicz LK, Morris S, Page JD, Sissons JGP (1983) Human cytomegalovirus specific cytotoxic T cells. Requirements for in vitro generation and specificity. Eur J Immunol 13: 804–809Google Scholar
  118. 118.
    Borysiewicz LK, Graham S, Hickling JK, Sissons JGP (1988) Precursor frequency and stage specificity of human cytomegalovirus specific cytotoxic T cells. Eur J Immunol 18: 269–275PubMedGoogle Scholar
  119. 119.
    Borysiewicz LK, Hickling JK, Graham S et al. (1988) Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72kd immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. J Exp Med 168: 919–931PubMedGoogle Scholar
  120. 120.
    Liu Y-NC, Klaus A, Kari B et al. (1991) The N-terminal 513 amino acids of the envelope glycoprotein gB of human cytomegalovirus stimulates both B- and T-cell immune responses in humans. J Virol 65: 1644–1648PubMedGoogle Scholar
  121. 121.
    Alp NJ, Allport TD, van Zanten J et al. (1991) Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein. J Virol 65: 4812–4820PubMedGoogle Scholar
  122. 122.
    Riddell SR, Rabin M, Geballe AP et al. (1991) Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression. J Immunol 146: 2795–2804PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Gary S. Marshall
    • 1
  • Stanley A. Plotkin
    • 2
    • 3
    • 4
  1. 1.Department of PediatricsUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Pasteur-Merieux Serums et VaccinsMarnes-la-CoquetteFrance
  3. 3.Connaught LaboratoriesSwiftwaterUSA
  4. 4.WillowdaleCanada

Personalised recommendations