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Journal of Virology, January 2003, p. 1049-1058, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1049-1058.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Prevention of Disease Induced by a Partially Heterologous AIDS Virus in Rhesus Monkeys by Using an Adjuvanted Multicomponent Protein Vaccine

Gerald Voss,1* Kelledy Manson,2 David Montefiori,3 David I. Watkins,4 Jonathan Heeney,5 Michael Wyand,2 Joe Cohen,1 and Claudine Bruck1

GlaxoSmithKline Biologicals, Rixensart, Belgium,1 Primedica Laboratories, Worcester, Massachusetts,2 Duke University Medical Center, Durham, North Carolina,3 Wisconsin Regional Primate Research Center, Madison, Wisconsin,4 Biomedical Primate Research Center, Rijswijk, The Netherlands5

Received 22 July 2002/ Accepted 21 October 2002

Recombinant protein subunit AIDS vaccines have been based predominantly on the virus envelope protein. Such vaccines elicit neutralizing antibody responses that can provide type-specific sterilizing immunity, but in most cases do not confer protection against divergent viruses. In this report we demonstrate that a multiantigen subunit protein vaccine was able to prevent the development of disease induced in rhesus monkeys by a partially heterologous AIDS virus. The vaccine was composed of recombinant human immunodeficiency virus type 1 (HIV-1) gp120, NefTat fusion protein, and simian immunodeficiency virus (SIV) Nef formulated in the clinically tested adjuvant AS02A. Upon challenge of genetically unselected rhesus monkeys with the highly pathogenic and partially heterologous SIV/HIV strain SHIV89.6p the vaccine was able to reduce virus load and protect the animals from a decline in CD4-positive cells. Furthermore, vaccination prevented the development of AIDS for more than 2.5 years. The combination of the regulatory proteins Nef and Tat together with the structural protein gp120 was required for vaccine efficacy.

* Corresponding author. Mailing address: Research & Development, GlaxoSmithKline Biologicals, Rue de l'Institut 89, 1330 Rixensart, Belgium. Phone: 32 (0)2 656 8243. Fax: 32 (0)2 656 9009. E-mail: gerald.voss{at}gskbio.com.

Journal of Virology, January 2003, p. 1049-1058, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1049-1058.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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Copyright © 2003 by the American Society for Microbiology. All rights reserved.