Abstract
AbstractEbola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50–90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping a Th1-biased adaptive immune response. GLA-SE adjuvanted mice and those adjuvanted with the SE component are better protected from surrogate challenge, while Th2 alum adjuvanted mice are not. Additionally, the immune response to FILORAB1 is long-lasting, as exhibited by highly-maintained serum antibody titers and long-lived cells in the spleen and bone marrow.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Infectious Diseases,Pharmacology,Immunology
Cited by
4 articles.
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