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Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice

Sunay, Melek M.E., Martins, Karen A.O., Steffens, Jesse T., Gregory, Melissa, Vantongeren, Sean A., Van Hoeven, Neal, Garnes, Preston G., Bavari, Sina
Vaccine 2019 v.37 no.29 pp. 3902-3910
Ebolavirus, T-lymphocytes, Toll-like receptor 4, adjuvants, agonists, animal models, antibodies, emulsions, glycoproteins, immune response, immunogenicity, lipids, mice, vaccination, virus-like particle vaccines
The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. The Ebola virus-like particle (VLP) vaccine expressing Ebola virus glycoprotein (GP) and matrix protein (VP40) was used in this study to evaluate the ability of TLR4 agonist glucopyranosyl lipid adjuvant (GLA) formulated in a stable emulsion (SE) to enhance immunogenicity and promote durable protection against mouse-adapted Ebola virus (ma-EBOV). Antibody responses and Ebola-specific T cell responses were evaluated post vaccination. Survival analysis after lethal ma-EBOV challenge was performed 4 weeks and 22 weeks following final vaccination. GLA-SE enhanced EBOV-specific immunity and resulted in long-term protection against challenge with ma-EBOV infection in a mouse model. Specifically, GLA-SE elicited Th1-skewed antibodies and promoted the generation of EBOV GP-specific polyfunctional T cells. These results provide further support for the utility of TLR4 activating GLA-SE-adjuvanted vaccines.