Adjuvant selection impacts the correlates of vaccine protection against Ebola infection

Abstract

The establishment of correlates of protection is particularly relevant in the context of rare, highly lethal pathogens such as filoviruses. We previously demonstrated that an Ebola glycoprotein virus-like particle (VLP) vaccine, when given as two intramuscular doses, conferred protection from challenge in a murine challenge model. In this study, we compared the ability of Advax inulin-based adjuvant formulations (Advax1-4) to enhance Ebola VLP vaccine protection in mice. After two immunizations, Advax-adjuvants that included a TLR9 agonist component induced high IgG responses, with complete protection against Ebola virus challenge. Although anti-Ebola IgG levels waned over time, protection was durable and was still evident 150 days post-immunization. Mice were protected after just a single VLP immunization with Advax-2 or -4 adjuvants. Advax-adjuvanted VLPs induced a stronger IFN-γ, TNF and IL-12 signature and serum transferred from Advax-adjuvanted vaccinees was able to transfer protection to naïve animals, showing that Ebola protection can be achieved by antibodies in the absence of cellular immunity. By contrast, serum from vaccinees incorporating a pICLC adjuvant did not transfer protection despite high IgG levels on ELISA. These data highlight the importance of adjuvant selection for development of a successful Ebola VLP vaccine.