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Journal of Virology, March 2005, p. 2956-2963, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2956-2963.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Multiclade Human Immunodeficiency Virus Type 1 Envelope Immunogens Elicit Broad Cellular and Humoral Immunity in Rhesus Monkeys

Michael S. Seaman,1 Ling Xu,2 Kristin Beaudry,1 Kristi L. Martin,1 Margaret H. Beddall,1 Ayako Miura,1 Anna Sambor,2 Bimal K. Chakrabarti,2 Yue Huang,2 Robert Bailer,2 Richard A. Koup,2 John R. Mascola,2 Gary J. Nabel,2 and Norman L. Letvin1,2*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts,1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland2

Received 2 August 2004/ Accepted 12 October 2004

The development of a human immunodeficiency virus type 1 (HIV-1) vaccine that elicits potent cellular and humoral immune responses recognizing divergent strains of HIV-1 will be critical for combating the global AIDS epidemic. The present studies were initiated to examine the magnitude and breadth of envelope (Env)-specific T-lymphocyte and antibody responses generated by vaccines containing either a single or multiple genetically distant HIV-1 Env immunogens. Rhesus monkeys were immunized with DNA prime-recombinant adenovirus boost vaccines encoding a Gag-Pol-Nef polyprotein in combination with either a single Env or a mixture of clade-A, clade-B, and clade-C Envs. Monkeys receiving the multiclade Env immunization developed robust immune responses to all vaccine antigens and, importantly, a greater breadth of Env recognition than monkeys immunized with vaccines including a single Env immunogen. All groups of vaccinated monkeys demonstrated equivalent immune protection following challenge with the pathogenic simian-human immunodeficiency virus 89.6P. These data suggest that a multicomponent vaccine encoding Env proteins from multiple clades of HIV-1 can generate broad Env-specific T-lymphocyte and antibody responses without antigenic interference. This study demonstrates that it is possible to generate protective immune responses by vaccination with genetically diverse isolates of HIV-1.

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

Journal of Virology, March 2005, p. 2956-2963, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2956-2963.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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