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Journal of Virology, November 2002, p. 11484-11490, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11484-11490.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Elicitation of Simian Immunodeficiency Virus-Specific Cytotoxic T Lymphocytes in Mucosal Compartments of Rhesus Monkeys by Systemic Vaccination

Jamal Baig,1 Daniel B. Levy,1 Paul F. McKay,1 Joern E. Schmitz,1 Sampa Santra,1 Ramu A. Subbramanian,1 Marcelo J. Kuroda,1 Michelle A. Lifton,1 Darci A. Gorgone,1 Linda S. Wyatt,2 Bernard Moss,2 Yue Huang,3 Bimal K. Chakrabarti,3 Ling Xu,3 Wing-Pui Kong,3 Zhi-Yong Yang,3 John R. Mascola,3 Gary J. Nabel,3 Angela Carville,4 Andrew A. Lackner,5 Ronald S. Veazey,5 and Norman L. Letvin1*

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445,2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-3005,3 New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,4 Tulane Regional Primate Research Center, Covington, Louisiana 704335

Received 22 April 2002/ Accepted 26 July 2002

Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymphocytes (CTL) specific for simian immunodeficiency virus (SIV) and simian HIV can be reproducibly sampled from intestinal mucosal tissue of rhesus monkeys obtained under endoscopic guidance. These lymphocytes recognize peptide-major histocompatibility complex class I complexes and express gamma interferon on exposure to peptide antigen. Interestingly, systemic immunization of monkeys with plasmid DNA immunogens followed by live recombinant attenuated poxviruses or adenoviruses with genes deleted elicits high-frequency SIV-specific CTL responses in these mucosal tissues. These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, BIDMC, 330 Brookline Ave., RE-113, Boston, MA 02215. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}caregroup.harvard.edu.

Journal of Virology, November 2002, p. 11484-11490, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11484-11490.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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