Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity

Thomas P. Monath, Cynthia K. Lee, Justin G. Julander, Alicja Brown, David W. Beasley, Douglas M. Watts, Edward Hayman, Patrick Guertin, Joseph Makowiecki, Joseph Crowell, Philip Levesque, Gavin C. Bowick, Merribeth Morin, Elizabeth Fowler, Dennis Trent

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with β-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX®, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX® [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P < 0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX® were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.

Original languageEnglish (US)
Pages (from-to)3827-3840
Number of pages14
JournalVaccine
Volume28
Issue number22
DOIs
StatePublished - May 14 2010

Keywords

  • Immune response
  • Inactivated vaccine
  • Yellow fever

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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  • Cite this

    Monath, T. P., Lee, C. K., Julander, J. G., Brown, A., Beasley, D. W., Watts, D. M., Hayman, E., Guertin, P., Makowiecki, J., Crowell, J., Levesque, P., Bowick, G. C., Morin, M., Fowler, E., & Trent, D. (2010). Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity. Vaccine, 28(22), 3827-3840. https://doi.org/10.1016/j.vaccine.2010.03.023