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Article
Nature Medicine  7, 1320 - 1326 (2001)
doi:10.1038/nm1201-1320

Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques

Igor M. Belyakov1, Zdenek Hel2, Brian Kelsall3, Vladimir A. Kuznetsov4, Jeffrey D. Ahlers1, Janos Nacsa2, David I. Watkins5, Todd M. Allen5, Alessandro Sette6, John Altman7, Ruth Woodward8, Phillip D. Markham8, John D. Clements9, Genoveffa Franchini2, Warren Strober3 & Jay A. Berzofsky1

1  Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Bethesda, Maryland, USA

2  Animal Model and Retroviral Vaccines Section, Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland, USA

3  Mucosal Immunity Section, Laboratory Of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA

4  Section of Medical Biophysics, Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland, USA

5  Wisconsin Regional Primate Research Center, Madison, Wisconsin, USA

6  Epimmune, San Diego, California, USA

7  Emory University Vaccine Center at Yerkes, Atlanta, Georgia, USA

8  Advanced BioScience Laboratories, Kensington, Maryland, USA

9  Department of Microbiology and Immunology, Program in Molecular Pathogenesis and Immunity, Tulane University School of Medicine, New Orleans, Louisiana, USA

Correspondence should be addressed to Jay A. Berzofsky berzofsk@helix.nih.gov or Igor M. Belyakov belyakov@box-b.nih.gov
Given the mucosal transmission of HIV-1, we compared whether a mucosal vaccine could induce mucosal cytotoxic T lymphocytes (CTLs) and protect rhesus macaques against mucosal infection with simian/human immunodeficiency virus (SHIV) more effectively than the same vaccine given subcutaneously. Here we show that mucosal CTLs specific for simian immunodeficiency virus can be induced by intrarectal immunization of macaques with a synthetic-peptide vaccine incorporating the LT(R192G) adjuvant. This response correlated with the level of T-helper response. After intrarectal challenge with pathogenic SHIV-Ku2, viral titers were eliminated more completely (to undetectable levels) both in blood and intestine, a major reservoir for virus replication, in intrarectally immunized animals than in subcutaneously immunized or control macaques. Moreover, CD4+ T cells were better preserved. Thus, induction of CTLs in the intestinal mucosa, a key site of virus replication, with a mucosal AIDS vaccine ameliorates infection by SHIV in non-human primates.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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