Journal
JOURNAL OF VIROLOGY
Volume 76, Issue 22, Pages 11659-11676Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.76.22.11659-11676.2002
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Funding
- NCRR NIH HHS [RR00164, K26 RR000168, P51 RR000168, P51 RR000164, RR00168] Funding Source: Medline
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As most human immunodeficiency virus (HIV) infection occurs via mucosal surfaces, an important goal of vaccination may be the induction of virus-specific immune responses at mucosal sites to contain viral infection early on. Here we designed a study in macaques carrying the major histocompatibility complex class I Mamu-A*01 molecule to assess the capacity of the highly attenuated poxvirus NWAC/simian immunodeficiency virus (SIV) SIVgpe vaccine candidate administered by the intranasal, intramuscular, or intrarectal route to induce mucosal immunity. All macaques, including one naive macaque, were exposed to SIVmac251 by the intrarectal route and sacrificed 48 h after infection. The kinetics of immune response at various time points following immunization with NWAC/SIVgpe and the anamnestic response to SIVmac251 at 48 h after challenge were assessed in blood, in serial rectal and vaginal biopsy samples, and in tissues at euthanasia with an SIVmac Gag-specific tetramer. In addition, at euthanasia, antigen-specific cells producing gamma interferon or tumor necrosis factor alpha from the jejunum lamina propria were quantified in all macaques. Surprisingly, antigenspecific CD8+ T cells were found in the mucosal tissues of all immunized macaques regardless of whether the vaccine was administered by a mucosal route (intranasal or intrarectal) or systemically. In addition, following mucosal SIVmac251 challenge, antigen-specific responses were mainly confined to mucosal tissues, again regardless of the route of immunization. We conclude that immunization with a live vector vaccine results in the appearance of CD8(+) T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes.
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