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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein
Journal of Immunology, Volume 174, No. 11, Year 2005
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Description
The utility of recombinant adenovirus serotype 5 (rAd5) vector-based vaccines for HIV-1 and other pathogens will likely be limited by the high prevalence of pre-existing Ad5-specific neutralizing Abs (NAbs) in human populations. However, the immunodominant targets of Ad5-specific NAbs in humans remain poorly characterized. In this study, we assess the titers and primary determinants of Ad5-specific NAbs in individuals from both the United States and the developing world. Importantly, median Ad5-specific NAb titers were > 10-fold higher in sub-Saharan Africa compared with the United States. Moreover, hexon-specific NAb titers were 4- to 10-fold higher than fiber-specific NAb titers in these cohorts by virus neutralization assays using capsid chimeric viruses. We next performed adoptive transfer studies in mice to evaluate the functional capacity of hexon- and fiber-specific NAbs to suppress the immunogenicity of a prototype rAd5-Env vaccine. Hexon-specific NAbs were remarkably efficient at suppressing Env-specific immune responses elicited by the rAd5 vaccine. In contrast, fiber-specific NAbs exerted only minimal suppressive effects on rAd5 vaccine immunogenicity. These data demonstrate that functionally significant Ad5-specific NAbs are directed primarily against the Ad5 hexon protein in both humans and mice. These studies suggest a potential strategy for engineering novel Ad5 vectors to evade dominant Ad5-specific NAbs. Copyright © 2005 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Lemckert, Angelique A.C.
Netherlands, Leiden
Crucell nv
Vogels, Ronald
Netherlands, Leiden
Crucell nv
Addo, Marylyn Martina
United States, Boston
Harvard Medical School
Lockman, Shahin
United States, Boston
Harvard T.h. Chan School of Public Health
Peter, Trevor F.
United States, Boston
Harvard T.h. Chan School of Public Health
Peyerl, Fred W.
United States, Boston
Beth Israel Deaconess Medical Center
Kishko, Michael G.
United States, Boston
Beth Israel Deaconess Medical Center
Gorgone, Darci A.
United States, Boston
Beth Israel Deaconess Medical Center
Lifton, Michelle A.
United States, Boston
Beth Israel Deaconess Medical Center
Essex, Myron E.
United States, Boston
Harvard T.h. Chan School of Public Health
Walker, Bruce D.
United States, Boston
Harvard Medical School
Goudsmit, Jaap
Netherlands, Leiden
Crucell nv
Havenga, Menzo J.E.
Netherlands, Leiden
Crucell nv
Barouch, Dan H.
United States, Boston
Beth Israel Deaconess Medical Center
Statistics
Citations: 303
Authors: 14
Affiliations: 4
Identifiers
Doi:
10.4049/jimmunol.174.11.7179
ISSN:
00221767
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study