|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
11
|
|
pubmed:dateCreated |
2005-5-20
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
pubmed-author:AddoMarylyn MMM,
pubmed-author:BarouchDan HDH,
pubmed-author:CustersJerome H H VJH,
pubmed-author:EssexMyronM,
pubmed-author:GorgoneDarci ADA,
pubmed-author:GoudsmitJaapJ,
pubmed-author:HavengaMenzo J EMJ,
pubmed-author:JacksonShawn SSS,
pubmed-author:KishkoMichael GMG,
pubmed-author:LemckertAngelique A CAA,
pubmed-author:LiftonMichelle AMA,
pubmed-author:LockmanShahinS,
pubmed-author:PeterTrevorT,
pubmed-author:PeyerlFred WFW,
pubmed-author:SumidaShawn MSM,
pubmed-author:TruittDiana MDM,
pubmed-author:VogelsRonaldR,
pubmed-author:WalkerBruce DBD
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
174
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
7179-85
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:15905562-Adenoviruses, Human,
pubmed-meshheading:15905562-Adult,
pubmed-meshheading:15905562-Animals,
pubmed-meshheading:15905562-Antibodies, Viral,
pubmed-meshheading:15905562-Capsid Proteins,
pubmed-meshheading:15905562-Dose-Response Relationship, Immunologic,
pubmed-meshheading:15905562-Genetic Vectors,
pubmed-meshheading:15905562-Humans,
pubmed-meshheading:15905562-Immunodominant Epitopes,
pubmed-meshheading:15905562-Immunosuppressive Agents,
pubmed-meshheading:15905562-Mice,
pubmed-meshheading:15905562-Mice, Inbred BALB C,
pubmed-meshheading:15905562-Mice, Inbred C57BL,
pubmed-meshheading:15905562-Neutralization Tests,
pubmed-meshheading:15905562-Seroepidemiologic Studies,
pubmed-meshheading:15905562-Vaccines, DNA,
pubmed-meshheading:15905562-Viral Vaccines
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein.
|
|
pubmed:affiliation |
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
