Mechanisms of immunity in post-exposure vaccination against Ebola virus infection

Steven B Bradfute; Scott M Anthony; Kelly S Stuthman; Natarajan Ayithan; Prafullakumar Tailor; Carl I Shaia; Mike Bray; Keiko Ozato; Sina Bavari

doi:10.1371/journal.pone.0118434

Back

Mechanisms of immunity in post-exposure vaccination against Ebola virus infection

Journal article

Open access

Peer reviewed

Mechanisms of immunity in post-exposure vaccination against Ebola virus infection

Steven B Bradfute, Scott M Anthony, Kelly S Stuthman, Natarajan Ayithan, Prafullakumar Tailor, Carl I Shaia, Mike Bray, Keiko Ozato and Sina Bavari

PloS one, Vol.10(3), pp.e0118434-e0118434

2015

DOI: 10.1371/journal.pone.0118434

PMCID: PMC4364937

PMID: 25785602

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0118434View

Published (Version of record) Open Access

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.

Animals

Cytokines - blood

Ebola Vaccines - immunology

Ebolavirus - immunology

Hemorrhagic Fever, Ebola - immunology

Hemorrhagic Fever, Ebola - prevention & control

Immunity

Mice

Mice, Knockout

Perforin - genetics

Post-Exposure Prophylaxis

Vaccination

Details

Title: Subtitle: Mechanisms of immunity in post-exposure vaccination against Ebola virus infection
Creators: Steven B Bradfute - United States Army Medical Research Institute of Infectious Diseases
Scott M Anthony - United States Army Medical Research Institute of Infectious Diseases
Kelly S Stuthman - United States Army Medical Research Institute of Infectious Diseases
Natarajan Ayithan - National Institutes of Health
Prafullakumar Tailor - Institute of Immunology
Carl I Shaia - United States Army Medical Research Institute of Infectious Diseases
Mike Bray - National Institutes of Health
Keiko Ozato - National Institutes of Health
Sina Bavari - United States Army Medical Research Institute of Infectious Diseases
Resource Type: Journal article
Publication Details: PloS one, Vol.10(3), pp.e0118434-e0118434
DOI: 10.1371/journal.pone.0118434
PMID: 25785602
PMCID: PMC4364937
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Language: English
Date published: 2015
Academic Unit: Pathology
Record Identifier: 9984185280602771

Metrics

13 Record Views

14 Times Cited - Web of Science

See more details