Progress in Vaccine Development for Prevention of Human Cytomegalovirus Infection

  • E. Gönczöl
  • S. Plotkin
Conference paper
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 154)


The infectious agent most frequently causing congenital malformations is the human cytomegalovirus (HCMV). HCMV infection is found in about 1% of newborns, and about 10%–15% of the infected children suffer either from immediate symptoms or late sequelae of the infection. Clinically apparent infections after birth are characterized by cytomegalic inclusion diseases (CIDs) in about 5% of the infected children. Another 5% have atypical involvement, usually with some damage of the CNS and 90% have no symptoms at birth. Among the most severely affected children mortality may be 30%. About 10%–15% of the children who are infected but asymptomatic at birth eventually develop mental retardation, chorioretinitis, microcephaly, and hearing loss (Weller 1971; Pass et al. 1980; Stagno et al. 1983, 1984).


Human Cytomegalovirus HCMV Infection Neutralization Titer Seropositive Individual Glycoprotein Complex 
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  1. Andersen HK (1970) Complement-fixing and virus-neutralizing antibodies in cytomegalovirus infection as measured against homologous and heterologous antigen. Acta Pathol Microbiol Immunol Scand 78: 504–508.Google Scholar
  2. Andersen HK (1971) Serologic differentiation of human cytomegalovirus strains using rabbit hyperimmune sera. Arch Gesamte Virusforsch 33: 187–191.PubMedCrossRefGoogle Scholar
  3. Ashley R, Mertz G, Clark H, Schick M, Salter D, Corey L (1985) Humoral immune response to herpes simplex virus type 2 glycoprotein in patients receiving a glycoprotein in subunit vaccine. J Virol 56:475–481.PubMedGoogle Scholar
  4. Borysiewicz LK, Hickling JK, Graham S, Sinclair J, Cranage MP, Smith GL, Sissons JGP (1988) Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specifc CTL recognizing the 72 kD immediate early protein and glycoprotein B-expressed by recombinant vaccinia viruses. J Exp Med 168:919–931.PubMedCrossRefGoogle Scholar
  5. Britt WJ (1984) Neutralizing antibodies detect a disulfide-linked glycoprotein complex within the envelope of human cytomegalovirus. Virology 135: 369–378.PubMedCrossRefGoogle Scholar
  6. Britt WJ, Auger D (1986) Synthesis and processing of the envelope gp 55-116 complex of human cytomegalovirus. J Virol 58: 185–191.PubMedGoogle Scholar
  7. Britt WJ, Vugler L, Stephens EB (1988) Induction of complement dependent and independent neutralizing antibodies by recombinant-derived human cytomegalovirus gp 55-116 (gB). J Virol 62: 3309–3318.PubMedGoogle Scholar
  8. Cranage MP, Kouzarides T, Bankier A, Satchwell S, Weston K, Tomlinson P, Barrell B, 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: 3057–3063.PubMedGoogle Scholar
  9. Cranage MP, Smith GL, Bell SE, Hart H, Brown C, Bankier AT, Tomlinson P, 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: 1416–1422.PubMedGoogle Scholar
  10. Elek SD, Stern H (1974) Development of a vaccine against mental retardation caused by cytomegalovirus infection in utero. Lancet 1:1–5.PubMedCrossRefGoogle Scholar
  11. Farrar GH, Greenaway PJ (1986) Characterization of glycoprotein complexes present in human cytomegalovirus envelopes. J Gen Virol 67: 1469–1473.PubMedCrossRefGoogle Scholar
  12. Farrar GH, Oram JD (1984) Characterization of the human cytomegalovirus envelope glycoprotein. J Gen Virol 65: 1991–2001.PubMedCrossRefGoogle Scholar
  13. Fleisher GR, Starr SE, Friedman HM, Plotkin SA (1982) Vaccination of pediatric nurses with live attenuated cytomegalovirus. Am J Dis Child 136: 294–296.PubMedGoogle Scholar
  14. Furlini G, Gönczöl E, Szokan G, Ianacone J, Plotkin SA (1987) Monoclonal antibodies directed to two groups of viral proteins neutralize human cytomegalovirus in vitro. Hybridoma 6: 321–326.PubMedCrossRefGoogle Scholar
  15. Furukawa T, Gönczöl E, Starr S, Tolpin MD, Arbeter A, Plotkin SA (1984) HCMV envelope antigens induce both humoral and cellular immunity in guinea pigs. Proc Soc Exp Biol Med 175: 243–250.PubMedGoogle Scholar
  16. Gibson W (1983) Protein counterparts of human and simian cytomegaloviruses. Virology 128: 391–406.PubMedCrossRefGoogle Scholar
  17. Gibson W, Irmiere A (1984) Selection of particles and proteins for use as human cytomegalovirus subunit vaccines. Birth Defects 20: 305–324.PubMedGoogle Scholar
  18. Glenn J (1981) Cytomegalovirus infections following renal transplantation. Rev Infect Dis 3: 1151–1178.PubMedCrossRefGoogle Scholar
  19. Gönczöl E, Andersen HK (1974) Studies on human cytomegalovirus strain variations by membrane-fluorescence. Arch Gesamte Virusforsch 44: 147–149.PubMedCrossRefGoogle Scholar
  20. Gönczöl E, Furlini G, Ianacone J, Plotkin SA (1986a) A rapid microneutralization assay for cytomegalovirus. J Virol Methods 14: 37–41.PubMedCrossRefGoogle Scholar
  21. Gönczöl E, Hudecz F, Ianacone J, Dietzschold B, Starr S, Plotkin SA (1986b) Immune responses to isolated human cytomegalovirus envelope proteins. J Virol 58: 661–664.PubMedGoogle Scholar
  22. Gönczöl E, Ianacone J, Furlini G, Ho W, Plotkin SA (1989a) Humoral immune response to cytomegalovirus Towne vaccine strain and to Toledo low passage strain. J Infect Dis (in press).Google Scholar
  23. Gönczöl E, Ianacone J, Ho W, Starr S, Meignier B, Plotkin SA (1989b) Subunit human cytomegalovirus (HCMV) vaccine induces humoral and cellular immune-responses in human volunteers. Vaccine (in press).Google Scholar
  24. Gretch DR, Gehrz RC, Stinski MF (1988a) Characterization of a human cytomegalovirus glycoprotein complex (gcI). J Gen Virol 69: 1205–1215.PubMedCrossRefGoogle Scholar
  25. Gretch DR, Kari B, Rasmussen L, Gehrz R, Stinski MF (1988b) Identification and characterization of three distinct families of glycoprotein complexes in the envelopes of human cytomegalovirus. J Virol 62:875–881.PubMedGoogle Scholar
  26. Gretch DR, Kari B, Gehrz RC, Stinski MF (1988c) A multigene family encodes the human cytomegalovirus glycoprotein complex gcII (gp 47-52 complex). J Virol 62: 1956–1962.PubMedGoogle Scholar
  27. Jonjic S, del Val M, Keil GM, Reddehase MJ, Koszinowski UH (1988) A nonstructural viral protein expressed by a recombinant vaccinia virus protects against lethal cytomegalovirus infection. J Virol 62: 1653–1658.PubMedGoogle Scholar
  28. Kari B, Lussenhop N, Goertz R, Wabuke-Burot M, Radeke M, Gehrz R (1986) Characterization of monoclonal antibodies reactive to several biochemically distinct human cytomegalovirus glycoprotein complexes. J Virol 60: 345–352.PubMedGoogle Scholar
  29. Landini MP, Michelson S (1988) Commented catalogue of human cytomegalovirus proteins. Prog Med Virol 35: 152–185.PubMedGoogle Scholar
  30. Liu Y-NC, Kari B, Gehrz RC (1988) Human immune responses to major human cytomegalovirus glycoprotein complexes. J Virol 62: 1066–1070.PubMedGoogle Scholar
  31. Mach M, Utz U, Fleckenstein B (1986) Mapping of the major glycoprotein gene of human cytomegalovirus. J Gen Virol 67: 1461–1467.PubMedCrossRefGoogle Scholar
  32. Masuho Y, Matsumoto Y, Sugano T, Fujinaga S, Minamishima Y (1987) Human monoclonal antibodies neutralizing human cytomegalovirus. J Gen Virol 68: 1457–1461.PubMedCrossRefGoogle Scholar
  33. Meyers JD, Leszczynski J, Zaia JA, Fluornoy N, Newton B, Snydman DR, Wright GG, et al. (1983) Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation. Ann Intern Med 98: 442–446.PubMedGoogle Scholar
  34. Nowak B, Sullivan C, Sarnow P, Thomas R, Bricout JC, Nicolas JC, Fleckenstein B, Levine AZ (1984) Characterization of monoclonal antibodies and polyclonal immune sera directed against human cytomegalovirus virion proteins. Virology 132: 325–338.PubMedCrossRefGoogle Scholar
  35. Pass RF, Stagno S, Myers GJ, Alford CA (1980) Outcome of symptomatic congenital cytomegalovirus infection: Results of long-term longitudinal follow-up. Pediatrics 66: 758–762.PubMedGoogle Scholar
  36. Pereira L, Hoffman M, Gallo D, Cremer N (1982) Monoclonal antibodies to human cytomegalovirus: three surface membrane proteins with unique immunological and electrophoretic properties specify cross-reactive determinants. Infect Immun 36: 924–932.PubMedGoogle Scholar
  37. Pereira L, Hoffman M, Tatsuno M, Dondero D (1984) Polymorphism of human cytomegalovirus glycoproteins characterized by monoclonal antibodies. Virology 139: 73–86.PubMedCrossRefGoogle Scholar
  38. Plotkin SA, Huang ES (1985) Cytomegalovirus vaccine virus (Towne strain) does not induce latency. J Infect Dis 152: 395–397.PubMedCrossRefGoogle Scholar
  39. Plotkin SA, Furukawa T, Zygraich N, Huygelen C (1975) Candidate cytomegalovirus strain for human vaccination. Infect Immun 12: 521–527.PubMedGoogle Scholar
  40. Plotkin SA, Farquhar J, Hornberger E (1976) Clinical trials of immunization with the Towne 125 strain of human cytomegalovirus. J Infect Dis 134: 470–475.PubMedCrossRefGoogle Scholar
  41. Plotkin SA, Friedman HM, Fleisher GR, Dafoe DC, Grossman RA, Smiley ML, Starr SE, et al. (1984) Towne vaccine induced prevention of cytomegalovirus disease after renal transplants. Lancet 1: 528–530.PubMedCrossRefGoogle Scholar
  42. Plotkin SA, Weibel RE, Alpert G, Starr SE, Friedman HM, Preblub SR, Hoxie J (1985) Resistance of seropositive volunteers to subcutaneous challenge with low passage human cytomegalovirus. J Infect Dis 151: 737–739.PubMedCrossRefGoogle Scholar
  43. Plotkin SA, Starr SE, Friedman HM, Gönczöl E (1989) Protective effects of Towne CMV vaccine against low passage CMV administered as a challenge. J Infect Dis (in press).Google Scholar
  44. Rasmussen L, Nelson R, Kelsall D, Merigan T (1984) M urine monoclonal antibody to a single protein neutralizes the infectivity of human cytomegalovirus. Proc Natl Acad Sci USA 81: 876–880.PubMedCrossRefGoogle Scholar
  45. Rasmussen L, Mullenax J, Nelson M, Merigan TC (1985a) Viral polypeptides detected by a complement-dependent neutralizing murine monoclonal antibody to human cytomegalovirus. J Virol 55: 274–280.PubMedGoogle Scholar
  46. Rasmussen L, Mullenax J, Nelson M, Merigan TC (1985b) Human cytomegalovirus polypeptides stimulate neutralizing antibody in vivo. Virology 145: 186–190.PubMedCrossRefGoogle Scholar
  47. Rasmussen L, Nelson M, Neff M, Merigan TC Jr (1988) Characterization of two different human cytomegalovirus glycoproteins which are targets for virus neutralizing antibody. Virology 163: 308–318.PubMedCrossRefGoogle Scholar
  48. Rodgers B, Borysiewicz L, Mundin J, Graham S, Sissons P (1987) Immunoaffinity purification of a 72 K early antigen of human cytomegalovirus: analysis of humoral and cell-mediated immunity to the purified polypeptide. J Gen Virol 68: 2371–2378.PubMedCrossRefGoogle Scholar
  49. Spaete RS, Thayer RM, Probert WS, Masiarz FR, Chamberlain SH, Rasmussen L, Merigan TC, Pachl C (1988) Virology 167: 207–225.PubMedCrossRefGoogle Scholar
  50. Stagno S, Pass RF, Dworsky ME, Alford CA (1983) Congenital and perinatal cytomegalovirus infections. Semin Perinatol 7: 31–42.PubMedGoogle Scholar
  51. Stagno S, Pass RF, Dworsky ME, Britt WJ, Alford CA (1984) Congenital and perinatal cytomegalovirus infections: clinical characteristics and pathogenic factors. Birth Defects 20: 65–85.PubMedGoogle Scholar
  52. Starr SE, Dalton B, Garrabrant T, Paucker K, Plotkin SA (1980) Lymphocyte blastogenesis and interferon production in adult leukocyte cultures stimulated with cytomegalovirus antigens. Infect Immun 30: 17–22.PubMedGoogle Scholar
  53. Starr SE, Glazer LP, Friedman HM, Farquhar JD, Plotkin SA (1981) Specific cellular and humoral immunity after immunization with live Towne strain cytomegalovirus vaccine. J Infect Dis 143: 585–589.PubMedCrossRefGoogle Scholar
  54. Weller TH (1971) The cytomegalovirus: ubiquitous agents with protean clinical manifestations. N Engl J Med 285: 203–214.PubMedCrossRefGoogle Scholar
  55. Winston DJ, Ho WG, Lin C-H, Budinger MD, Champlin RE, Gale RP (1984) Intravenous immunoglobulin for modification of cytomegalovirus infections associated with bone marrow transplantation: preliminary results of a controlled trial. Am J Med 76: 128–133.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • E. Gönczöl
    • 1
  • S. Plotkin
    • 1
  1. 1.The Wistar InstitutePhiladelphiaUSA

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