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Successful DNA immunization against measles: Neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles

Nature Medicine volume 6, pages 776–781 (2000)Cite this article

An Erratum to this article was published on 01 September 2000

Abstract

Measles remains a principal cause of worldwide mortality, in part because young infants cannot be immunized effectively. Development of new vaccines has been hindered by previous experience with a formalin-inactivated vaccine that predisposed to a severe form of disease (atypical measles). Here we have developed and tested potential DNA vaccines for immunogenicity, efficacy and safety in a rhesus macaque model of measles. DNA protected from challenge with wild-type measles virus. Protection correlated with levels of neutralizing antibody and not with cytotoxic T lymphocyte activity. There was no evidence in any group, including those receiving hemagglutinin-encoding DNA alone, of ‘priming’ for atypical measles.

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Figure 1: Immune responses to vaccination and boosting with DNA plasmids encoding H and/or F MV proteins by intradermal injection or gene-gun inoculation in rhesus macaques.
Figure 2: Skin responses to MV infection. Left, DNA-vaccinated monkey (1J); right, unimmunized monkey (16H).
Figure 3: Detection of MV by PCR in the blood of immunized monkeys after challenge with wild-type MV.
Figure 4: Immune responses to MV challenge in naive monkeys and monkeys pre-immunized with live and DNA vaccines.

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References

  1. Albrecht, P., Ennis, F.A., Saltzman, E.J. & Krugman, S. Persistence of maternal antibody in infants beyond 12 months: Mechanism of measles vaccine failure. J. Pediatr. 91, 715–178 (1977).

    Article  CAS  Google Scholar 

  2. Gans, H.A. et al. Deficiency of the humoral immune response to measles vaccine in infants immunized at age 6 months. J. Am. Med. Assoc. 280, 527–532 (1998).

    Article  CAS  Google Scholar 

  3. Holt, E.A., Moulton, L.H., Siberry, G.K. & Halsey, N.A. Differential mortality by measles vaccine titer and sex. J. Infect. Dis. 168, 1087–1096 ( 1993).

    Article  CAS  Google Scholar 

  4. Berry, S. et al. Comparison of high titer Edmonston-Zagreb, Biken-CAM and Schwarz measles vaccines in Peruvian infants. Ped. Infect. Dis. J. 11, 822–827 (1992).

    Article  CAS  Google Scholar 

  5. Garenne, M., Leroy, O., Beau, J.-P. & Sene, I. Child mortality after high-titre measles vaccines:prospective study in Senegal. Lancet 338, 903–907 ( 1991).

    Article  CAS  Google Scholar 

  6. Annunziato, D. et al. Atypical measles syndrome: Pathologic and serologic findings . Pediatrics 70, 203–209 (1982).

    CAS  PubMed  Google Scholar 

  7. Nader, P.R., Horwitz, M.S. & Rousseau, J. Atypical exanthem following exposure to natural measles: Eleven cases in children previously inoculated with killed vaccine. J. Pediatr. 72, 22–28 ( 1968).

    Article  Google Scholar 

  8. Fulginiti, V.A., Eller, J.J., Downie, A.W. & Kempe, C.H. Altered reactivity to measles virus: Atypical measles in children previously immunized with inactivated measles virus vaccines. J. Am. Med. Assoc. 202, 1075 (1967).

  9. Norrby, E., Enders-Ruckle, G. & ter Meulen, V. Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus . J. Infect. Dis. 132, 262– 269 (1975).

    Article  CAS  Google Scholar 

  10. Norrby, E. & Gollmar, Y. Identification of measles virus-specific hemolysis-inhibiting antibodies separate from hemagglutination-inhibiting antibodies. Infect. Immun. 11, 231– 239 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Merz, D.C., Scheid, A. & Choppin, P.W. Importance of antibodies to the fusion glycoprotein of paramyxoviruses in the prevention of spread of infection. J. Exp. Med. 151, 275–288 ( 1980).

    Article  CAS  Google Scholar 

  12. Auwaerter, P.G. et al. Measles virus infection in rhesus macaques: Altered immune responses and comparison of the virulence of six different virus strains. J. Infect. Dis. 180, 950–958 (1999).

    Article  CAS  Google Scholar 

  13. Polack, F.P. et al. Production of atypical measles in rhesus macaques: evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody. Nature Med. 5, 629–634 (1999).

    Article  CAS  Google Scholar 

  14. Lodmell, D.L. et al. DNA immunization protects nonhuman primates against rabies virus. Nature Med. 4, 949– 952 (1998).

    Article  CAS  Google Scholar 

  15. Yang, K. et al. Early studies on DNA-based immunizations for measles virus. Vaccine 15, 888–892 ( 1997).

    Article  CAS  Google Scholar 

  16. Drillien, R. et al. Protection of mice from fatal measles encephalitis by vaccination with vaccinia virus recombinants encoding either the hemagglutinin or the fusion protein. Proc. Natl. Acad. Sci. USA 85, 1252–1256 (1988).

    Article  CAS  Google Scholar 

  17. Giraudon, P. & Wild, T.F. Correlation between epitopes on hemagglutinin of measles virus and biological activities: passive protection by monoclonal antibodies is related to their hemagglutination inhibiting acitivity. Virology 144, 46–58 ( 1985).

    Article  CAS  Google Scholar 

  18. Malvoisin, E. & Wild, F. Contribution of measles virus fusion protein in protective immunity: anti-F monoclonal antibodies neutralize virus infectivity and protect mice against challenge. J. Virol. 64, 5160–5162 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Chen, R.T. et al. Measles antibody: reevaluation of protective titers. J. Infect. Dis. 162, 1036–1042 (1990).

    Article  CAS  Google Scholar 

  20. Damien, B., Huiss, S., Schneider, F. & Muller, C.P. Estimated susceptibility to asymptomatic secondary immune response against measles in late convalescent and vaccinated persons. J. Med. Virol. 56, 85–90 (1998).

    Article  CAS  Google Scholar 

  21. Etchart, N., Buckland, R., Liu, M.A., Wild, T.F. & Kaiserlian, D. Class I-restricted CTL induction by mucosal immunization with naked DNA encoding measles virus haemagglutinin. J. Gen. Virol. 78, 1577–1580 ( 1997).

    Article  CAS  Google Scholar 

  22. Fooks, A.R., Jeevarajah, D., Warnes, A., Wilkinson, G.W. & Clegg, J.C. Immunization of mice with plasmid DNA expressing the measles virus nucleoprotein gene. Viral Immunol. 9, 65–71 (1996 ).

    Article  CAS  Google Scholar 

  23. Cardoso, A.I. et al. Measles virus DNA vaccination: antibody isotype is determined by the method of immunization and by the nature of both the antigen and the coimmunized antigen. J. Virol. 72, 2516– 2518 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Cardoso, A.I. et al. Immunization with plasmid DNA encoding for the measles virus hemagglutinin and nucleoprotein leads to humoral and cell-mediated immunity . Virology 225, 293–299 (1996).

    Article  CAS  Google Scholar 

  25. Donnelly, J.J. et al. Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus. Nature Med. 1, 583–587 ( 1995).

    Article  CAS  Google Scholar 

  26. Davis, H.L., McCluskie, M.J., Gerin, J.L. & Purcell, R.H. DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proc. Natl. Acad. Sci. USA 93, 7213–7218 (1996).

    Article  CAS  Google Scholar 

  27. Robinson, H.L. et al. Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations . Nature Med. 5, 526–534 (1999).

    Article  CAS  Google Scholar 

  28. Condon, C., Watkins, S.C., Celluzzi, C.M., Thompson, K. & Falo, L.D. Jr. DNA-based immunization by in vivo transfection of dendritic cells. Nature Med. 2, 1122–1128 ( 1996).

    Article  CAS  Google Scholar 

  29. Raz, E. et al. Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Nat. Acad. Sci. USA 91, 9519–9523 ( 1994).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by research grant AI-35149 (D.E.G.), and training grants AI-07417 (A.V.) and AI-07541 (A.V.) from the National Institutes of Health and the Pasteur Mérieux Connaught Fellowship in Pediatrics (F.P.P.).

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Authors and Affiliations

  1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, 615 N. Wolfe Street, Baltimore, 21205, Maryland , USA

    Fernando P. Polack, Sok H. Lee, Sallie Permar, Elizabeth Manyara, Yaikah Jeng, Alexandra Valsamakis & Diane E. Griffin

  2. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, 21287 , Maryland, USA

    Fernando P. Polack

  3. Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, 21287 , Maryland, USA

    Hossein G. Nousari

  4. Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, 21287 , Maryland, USA

    Robert J. Adams

  5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 21287, Maryland, USA

    Alexandra Valsamakis

  6. Department of Molecular Microbiology and Immunology Emory University,, Atlanta, 30329, Georgia, USA

    Farah Mustafa & Harriet L. Robinson

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  1. Fernando P. Polack
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Correspondence to Diane E. Griffin.

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Polack, F., Lee, S., Permar, S. et al. Successful DNA immunization against measles: Neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles. Nat Med 6, 776–781 (2000). https://doi.org/10.1038/77506

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