Abstract
BackgroundChikungunya 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.MethodsNine 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.ResultsThe 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.ConclusionsThese 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.
Highlights
MethodsNine cynomolgus macaques were immunized and boosted with the measles virus-vectored chikungunya vaccine or sham-vaccinated
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
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
Summary
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. Adult cynomolgus macaques (4 males and 5 females) weighing 2.7–3.2 kg and determined to be alphavirus antibody-free based on hemagglutination inhibition assays for western, eastern, and Venezuelan equine encephalitis viruses, CHIKV, Sindbis, and Semliki Forest viruses, and MV were obtained from Covance (Alice, TX). The animals were quarantined for 14 days. A veterinarian conducted a physical examination of each animal during the quarantine period to ensure the animals’ health and implanted the animals with TA10TA-D70 telemetry transponders (Data Sciences International, St. Paul, MN)
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