Prevention of disease induced by a partially heterologous AIDS virus in rhesus monkeys by using an adjuvanted multicomponent protein vaccine.
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 SHIV(89.6p) 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.
Voss
Gerald
G
GlaxoSmithKline Biologicals, Rixensart, Belgium. gerald.voss@gskbio.com
Manson
Kelledy
K
Montefiori
David
D
Watkins
David I
DI
Heeney
Jonathan
J
Wyand
Michael
M
Cohen
Joe
J
Bruck
Claudine
C
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D008253:Macaca mulatta; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D019562:Viral Load
D016915:AIDS Vaccines; D015483:HIV Antibodies