Document Detail

Replicating adenovirus-simian immunodeficiency virus (SIV) vectors efficiently prime SIV-specific systemic and mucosal immune responses by targeting myeloid dendritic cells and persisting in rectal macrophages, regardless of immunization route.
MedLine Citation:
PMID:  22441384     Owner:  NLM     Status:  MEDLINE    
Although priming with replicating adenovirus type 5 host range mutant (Ad5hr)-human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) recombinants, followed by HIV/SIV envelope boosting, has proven highly immunogenic, resulting in protection from SIV/simian-human immunodeficiency virus (SHIV) challenges, Ad5hr recombinant distribution, replication, and persistence have not been examined comprehensively in nonhuman primates. We utilized Ad5hr-green fluorescent protein and Ad5hr-SIV recombinants to track biodistribution and immunogenicity following mucosal priming of rhesus macaques by the intranasal/intratracheal, sublingual, vaginal, or rectal route. Ad recombinants administered by all routes initially targeted macrophages in bronchoalveolar lavage (BAL) fluid and rectal tissue, later extending to myeloid dendritic cells in BAL fluid with persistent expression in rectal mucosa 25 weeks after the last Ad immunization. Comparable SIV-specific immunity, including cellular responses, serum binding antibody, and mucosal secretory IgA, was elicited among all groups. The ability of the vector to replicate in multiple mucosal sites irrespective of delivery route, together with the targeting of macrophages and professional antigen-presenting cells, which provide potent immunogenicity at localized sites of virus entry, warrants continued use of replicating Ad vectors.
L Jean Patterson; Seraphin Kuate; Mara Daltabuit-Test; Qingsheng Li; Peng Xiao; Katherine McKinnon; Janet DiPasquale; Anthony Cristillo; David Venzon; Ashley Haase; Marjorie Robert-Guroff
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-03-21
Journal Detail:
Title:  Clinical and vaccine immunology : CVI     Volume:  19     ISSN:  1556-679X     ISO Abbreviation:  Clin. Vaccine Immunol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-08-15     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101252125     Medline TA:  Clin Vaccine Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  629-37     Citation Subset:  IM    
Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
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MeSH Terms
Adenoviruses, Human / genetics*
Administration, Intranasal
Administration, Intravaginal
Administration, Rectal
Administration, Sublingual
Antibodies, Viral / blood
Dendritic Cells / immunology*
Genetic Vectors*
Immunoglobulin A, Secretory / analysis
Leukocytes, Mononuclear / immunology
Macaca mulatta
Macrophages / immunology*
SAIDS Vaccines / administration & dosage,  genetics,  immunology*
Simian immunodeficiency virus / genetics,  immunology*
Vaccines, Synthetic / administration & dosage,  genetics,  immunology
Reg. No./Substance:
0/Antibodies, Viral; 0/Immunoglobulin A, Secretory; 0/SAIDS Vaccines; 0/Vaccines, Synthetic

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