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

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)629-637
Number of pages9
JournalClinical and Vaccine Immunology
Volume19
Issue number5
DOIs
StatePublished - May 1 2012

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Immunization
Simian Immunodeficiency Virus
Mucosal Immunity
Macrophages
Myeloid Cells
Viruses
Adenoviridae
Dendritic Cells
Host Specificity
Bronchoalveolar Lavage Fluid
HIV
Secretory Immunoglobulin A
Virus Internalization
Antigen-Presenting Cells
Green Fluorescent Proteins
Macaca mulatta
Cellular Immunity
Primates
Mucous Membrane
Fluids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

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. / Patterson, L. Jean; Kuate, Seraphin; Daltabuit-Test, Mara; Li, Qingsheng; Xiao, Peng; McKinnon, Katherine; DiPasquale, Janet; Cristillo, Anthony; Venzon, David; Haase, Ashley; Robert-Guroff, Marjorie.

In: Clinical and Vaccine Immunology, Vol. 19, No. 5, 01.05.2012, p. 629-637.

Research output: Contribution to journalArticle

Patterson, L. Jean ; Kuate, Seraphin ; Daltabuit-Test, Mara ; Li, Qingsheng ; Xiao, Peng ; McKinnon, Katherine ; DiPasquale, Janet ; Cristillo, Anthony ; Venzon, David ; Haase, Ashley ; Robert-Guroff, Marjorie. / 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. In: Clinical and Vaccine Immunology. 2012 ; Vol. 19, No. 5. pp. 629-637.
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