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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice
Journal of Virology, Volume 82, No. 14, Year 2008
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Description
The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit small-pox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia virus intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia virus challenge model. A single immunization with the rAd35-L1R vector effectively protected mice against a lethal systemic vaccinia virus challenge. The rAd35-L1R vector also proved more efficacious than the combination of four rAd35 vectors expressing A27L, L1R, A33R, and B5R. Moreover, serum containing LIR-specific neutralizing antibodies afforded postexposure prophylaxis after systemic vaccinia virus infection. In contrast, the combination of rAd35-L1R and rAd35-B5R vectors was required to protect mice against a lethal intranasal vaccinia virus challenge, suggesting that both IMV- and EEV-specific immune responses are important following intranasal infection. Taken together, these data demonstrate that different protective antigens are required based on the route of vaccinia virus challenge. These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Goudsmit, Jaap
Netherlands, Leiden
Crucell nv
Holterman, Lennart
Netherlands, Leiden
Crucell nv
Ewald, Bonnie A.
United States, Boston
Beth Israel Deaconess Medical Center
Héraud, Jean Michel
United States, Bethesda
National Institutes of Health Nih
Franchini, Genoveffa
United States, Bethesda
National Institutes of Health Nih
Seaman, Michael S.
United States, Boston
Beth Israel Deaconess Medical Center
Havenga, Menzo J.E.
Netherlands, Leiden
Crucell nv
Barouch, Dan H.
United States, Boston
Beth Israel Deaconess Medical Center
Statistics
Citations: 33
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1128/JVI.00353-08
ISSN:
0022538X
Research Areas
Maternal And Child Health