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Journal of Virology, November 2002, p. 11659-11676, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11659-11676.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIVgpe Recombinant Vaccine Result in Gag-Specific CD8+ T-Cell Responses in Mucosal Tissues of Macaques

Liljana Stevceva,1 Xavier Alvarez,2,{dagger} Andrew A. Lackner,2,{dagger} Elzbieta Tryniszewska,1 Brian Kelsall,3 Janos Nacsa,1 Jim Tartaglia,4 Warren Strober,2 and Genoveffa Franchini1*

Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892,1 Division of Comparative Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102,2 Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-1890,3 Aventis-Pasteur, Toronto, Ontario, Canada M2R 3T44

Received 11 April 2002/ Accepted 19 August 2002

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 NYVAC/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 NYVAC/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, antigen-specific 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.

* Corresponding author. Mailing address: National Cancer Institute, Basic Research Laboratory, 41/D804, Bethesda, MD 20892. Phone: (301) 496-2386. Fax: (301) 496-2386. E-mail: franchig{at}mail.nih.gov.

{dagger} Present address: Tulane Regional Primate Research Center, Covington, LA 70433.

Journal of Virology, November 2002, p. 11659-11676, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11659-11676.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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