Immunogenicity and Efficacy of a Measles Virus-Vectored Chikungunya Vaccine in Nonhuman Primates

J Infect Dis. 2019 Jul 31;220(5):735-742. doi: 10.1093/infdis/jiz202.

Abstract

Background: Chikungunya virus (CHIKV) infection can result in chikungunya fever (CHIKF), a self-limited acute febrile illness that can progress to chronic arthralgic sequelae in a large percentage of patients. A new measles virus-vectored vaccine was developed to prevent CHIKF, and we tested it for immunogenicity and efficacy in a nonhuman primate model.

Methods: Nine cynomolgus macaques were immunized and boosted with the measles virus-vectored chikungunya vaccine or sham-vaccinated. Sera were taken at multiple times during the vaccination phase to assess antibody responses against CHIKV. Macaques were challenged with a dose of CHIKV previously shown to cause fever and viremia, and core body temperature, viremia, and blood cell and chemistry panels were monitored.

Results: The vaccine was well tolerated in all macaques, and all seroconverted (high neutralizing antibody [PRNT80 titers, 40-640] and enzyme-linked immunosorbent assay titers) after the boost. Furthermore, the vaccinated primates were protected against viremia, fever, elevated white blood cell counts, and CHIKF-associated cytokine changes after challenge with the virulent La Reunión CHIKV strain.

Conclusions: These results further document the immunogenicity and efficacy of a measles-vectored chikungunya vaccine that shows promise in Phase I-II clinical trials. These findings are critical to human health because no vaccine to combat CHIKF is yet licensed.

Keywords: chikungunya virus; measles virus; nonhuman primate; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Body Temperature
  • Chikungunya Fever / prevention & control*
  • Chikungunya Fever / virology
  • Chikungunya virus / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Genetic Vectors
  • Humans
  • Immunization, Secondary
  • Immunogenicity, Vaccine / immunology*
  • Macaca fascicularis / immunology
  • Male
  • Measles / prevention & control*
  • Measles Vaccine / immunology*
  • Measles virus / immunology
  • Vaccination
  • Viral Vaccines / immunology*
  • Viremia

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Measles Vaccine
  • Viral Vaccines