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

Authors :
Shannan L. Rossi
William S Lawrence
Sabrina Schrauf
Jessica A. Plante
Eryu Wang
Jason E. Comer
Scott C. Weaver
Katrin Ramsauer
Sasha R. Azar
Source :
The Journal of Infectious Diseases
Publication Year :
2019
Publisher :
Oxford University Press (OUP), 2019.

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.<br />Chikungunya fever is a debilitating human disease. A measles-based vaccine expressing chikungunya proteins can protect nonhuman primates from disease, including fever, white blood cell count reduction, viremia, and proinflammatory cytokine levels. Lineage cross-reactive antibodies are also produced.

Details

ISSN :
15376613 and 00221899
Volume :
220
Database :
OpenAIRE
Journal :
The Journal of Infectious Diseases
Accession number :
edsair.doi.dedup.....729f78759959b5d9a7e19b0b436f7652
Full Text :
https://doi.org/10.1093/infdis/jiz202