title: Mechanisms of immunity in post-exposure vaccination against Ebola virus infection.
abstract: Ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. Although there is no clinically proven vaccine or treatment for Ebola virus infection, a virus-like particle (VLP) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. In this work, we report that VLPs protect Ebola virus-infected mice when given 24 hours post-infection. Analysis of cytokine expression in serum revealed a decrease in pro-inflammatory cytokine and chemokine levels in mice given VLPs post-exposure compared to infected, untreated mice. Using knockout mice, we show that VLP-mediated post-exposure protection requires perforin, B cells, macrophages, conventional dendritic cells (cDCs), and either CD4+ or CD8+ T cells. Protection was Ebola virus-specific, as marburgvirus VLPs did not protect Ebola virus-infected mice. Increased antibody production in VLP-treated mice correlated with protection, and macrophages were required for this increased production. However, NK cells, IFN-gamma, and TNF-alpha were not required for post-exposure-mediated protection. These data suggest that a non-replicating Ebola virus vaccine can provide post-exposure protection and that the mechanisms of immune protection in this setting require both increased antibody production and generation of cytotoxic T cells.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Bradfute
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Anthony
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Stuthman
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Ayithan
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Prafullakumar
authors.initials: P
authors.lastname: Tailor
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors.forename: Carl I
authors.initials: CI
authors.lastname: Shaia
authors.affiliation: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Mike
authors.initials: M
authors.lastname: Bray
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D046129:Ebola Vaccines / Q000276:immunology*; D029043:Ebolavirus / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D007109:Immunity; D051379:Mice; D018345:Mice, Knockout; D054353:Perforin / Q000235:genetics; D056990:Post-Exposure Prophylaxis; D014611:Vaccination
chemical_list: D016207:Cytokines; D046129:Ebola Vaccines; D054353:Perforin