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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2004-5-6
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pubmed:abstractText |
The high prevalence of pre-existing immunity to adenovirus serotype 5 (Ad5) in human populations may substantially limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for HIV-1 and other pathogens. A potential solution to this problem is to use vaccine vectors derived from adenovirus (Ad) serotypes that are rare in humans, such as Ad35. However, cross-reactive immune responses between heterologous Ad serotypes have been described and could prove a major limitation of this strategy. In particular, the extent of immunologic cross-reactivity between Ad5 and Ad35 has not previously been determined. In this study we investigate the impact of pre-existing anti-Ad5 immunity on the immunogenicity of candidate rAd5 and rAd35 vaccines expressing SIV Gag in mice. Anti-Ad5 immunity at levels typically found in humans dramatically blunted the immunogenicity of rAd5-Gag. In contrast, even high levels of anti-Ad5 immunity did not substantially suppress Gag-specific cellular immune responses elicited by rAd35-Gag. Low levels of cross-reactive Ad5/Ad35-specific CD4(+) T lymphocyte responses were observed, but were insufficient to suppress vaccine immunogenicity. These data demonstrate the potential utility of Ad35 as a candidate vaccine vector that is minimally suppressed by anti-Ad5 immunity. Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:ArthurJanelle CJC,
pubmed-author:BarouchDan HDH,
pubmed-author:CustersJerome H H VJH,
pubmed-author:GorgoneDarci ADA,
pubmed-author:GoudsmitJaapJ,
pubmed-author:HavengaMenzo J EMJ,
pubmed-author:KishkoMichael GMG,
pubmed-author:Korioth-SchmitzBirgitB,
pubmed-author:KostenseStefanS,
pubmed-author:KoudstaalWouterW,
pubmed-author:LetvinNorman LNL,
pubmed-author:LiftonMichelle AMA,
pubmed-author:NabelGary JGJ,
pubmed-author:NewbergMichael HMH,
pubmed-author:PanicaliDennis LDL,
pubmed-author:PauMaria GMG,
pubmed-author:SumidaShawn MSM,
pubmed-author:TruittDiana MDM
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
172
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6290-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15128818-Adenoviridae,
pubmed-meshheading:15128818-Adenoviridae Infections,
pubmed-meshheading:15128818-Amino Acid Sequence,
pubmed-meshheading:15128818-Animals,
pubmed-meshheading:15128818-CD8-Positive T-Lymphocytes,
pubmed-meshheading:15128818-Dose-Response Relationship, Immunologic,
pubmed-meshheading:15128818-Epitope Mapping,
pubmed-meshheading:15128818-Epitopes, T-Lymphocyte,
pubmed-meshheading:15128818-Gene Products, gag,
pubmed-meshheading:15128818-Genetic Vectors,
pubmed-meshheading:15128818-Immunity, Active,
pubmed-meshheading:15128818-Immunization, Secondary,
pubmed-meshheading:15128818-Immunization Schedule,
pubmed-meshheading:15128818-Injections, Intramuscular,
pubmed-meshheading:15128818-Mice,
pubmed-meshheading:15128818-Mice, Inbred BALB C,
pubmed-meshheading:15128818-Mice, Inbred C57BL,
pubmed-meshheading:15128818-Molecular Sequence Data,
pubmed-meshheading:15128818-Peptide Fragments,
pubmed-meshheading:15128818-Protein Binding,
pubmed-meshheading:15128818-Serotyping,
pubmed-meshheading:15128818-Simian immunodeficiency virus,
pubmed-meshheading:15128818-Vaccines, Synthetic,
pubmed-meshheading:15128818-Viral Vaccines
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pubmed:year |
2004
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pubmed:articleTitle |
Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity.
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pubmed:affiliation |
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. dbarouch@bidmc.harvard.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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