Vaccine-elicited immune responses prevent clinical AIDS in SHIV(89.6P)-infected rhesus monkeys.
Accumulating evidence has demonstrated the importance of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes in controlling HIV-1 replication. We have elicited immune responses in rhesus monkeys utilizing DNA vaccines augmented by the administration of IL-2/Ig, a fusion protein consisting of interleukin-2 and the Fc portion of IgG2. These vaccine-elicited immune responses did not prevent infection following a high-dose intravenous challenge with SHIV(89.6P) but did control viremia to nearly undetectable levels and prevented immunodeficiency and clinical disease. In contrast, control monkeys developed high levels of viremia and exhibited a rapid loss of CD4(+) T cells, significant clinical disease progression, and death in half of the animals by day 140 following challenge. Vaccine approaches that elicit immune responses capable of reducing plasma viral loads, but not capable of inducing sterilizing immunity, may still provide substantial clinical benefits.
Barouch
D H
DH
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. dan_barouch@hotmail.com
Fu
T M
TM
Montefiori
D C
DC
Lewis
M G
MG
Shiver
J W
JW
Letvin
N L
NL
D016915:AIDS Vaccines / Q000494:pharmacology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D018791:CD4 Lymphocyte Count; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008253:Macaca mulatta / Q000276:immunology*; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000494:pharmacology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control
D016915:AIDS Vaccines; D015483:HIV Antibodies; D007141:Immunoglobulin Fc Fragments; D007376:Interleukin-2; D018449:SAIDS Vaccines; D019444:Vaccines, DNA