A VLP vaccine for epidemic Chikungunya virus protects non-human primates against infection

Akahata, Wataru; Yang, Zhi-yong; Andersen, Hanne; Sun, Siyang; Holdaway, Heather A.; Kong, Wing-Pui; Lewis, Mark G.; Higgs, Stephen; Rossmann, Michael G.; Rao, Srinivas; Nabel, Gary J.

Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe, and Asia1,2 since its re-emergence in Kenya in 2004. The severity of disease and spread of this epidemic virus present a serious public health threat in the absence of vaccines or anti-viral therapies. Here, we describe a novel vaccine that protects against emerging CHIKV infection of non-human primates (NHP). We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from different CHIKV strains. Monkeys immunized with VLPs produced high titer neutralizing antibodies that protected against viremia after high dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, establishing a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.