Comparative Immunogenicities of Chikungunya Vaccines Prepared in Avian and Mammalian Tissues

Abstract

Summary The comparative immunogenicities of experimental formalin-inactivated chikungunya (CHIK) vaccines prepared in chick-embryo (CE), suckling-mouse-brain (SMB), and green-monkey kidney-cell (GMKC) tissue culture with the CHIK 168 virus have been described. Tests of protection in mice revealed that CE vaccine was markedly inferior to either SMB or GMKC vaccine. Both SMB and GMKC vaccine were highly effective in protecting mice against an intracerebral challenge. However, the potentially encephalitogenic properties of SMB vaccines seriously limit their use in practice, so further evaluation of this vaccine was not now pursued. Results of plaque-inhibition tests revealed that GMKC vaccine elicited significant levels of serum-neutralization (N) antibody in mice to heterologous African E-103, Asian BAH-306, and Indian C-266 strains as well as the homologous 168 strain of CHIK virus. To correlate these findings with actual protection a vaccine trial was performed in rhesus monkeys, with these strains of the CHIK virus in the challenge procedure. After three doses of GMKC vaccine, high levels of N antibody developed in monkeys, and in most instances, CF and HI antibody were present in low titers to the challenge viruses. The immunogenic potency of GMKC vaccine was clearly defined by the complete absence of viremia in the vaccinated monkeys and no appreciable stimulation of N, complement-fixation, or hemagglutination-inhibition antibody subsequent to challenge. In contrast, the control monkeys, with one exception, had viremia, and responded with high levels of N, CF, and HI antibody after challenge.