SHIV Infection Protects Against Heterologous Pathogenic SHIV Challenge in Macaques: A Gold-Standard for HIV-1 Vaccine Development?
Robert Sealy, Xiaoyan Zhan, Timothy D. Lockey, Louis Martin, James Blanchard, Vicki Traina-Dorge and Julia L. Hurwitz
Pages 497-503 (7)
A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argument is that protection from superinfection is significant, reflecting a robust immune response that might be harnessed by vaccination to prevent disease. In an experiment designed to address the debate, two macaques received an I.V. inoculation with SHIV KU-1-d (a derivative of SHIV KU-1) and were rested for > 10 months. Infection elicited diverse neutralizing antibody activities in both animals. Animals were then exposed to SHIV 89.6P (I.V.), a virus carrying a heterologous envelope protein relative to the vaccine strain. Infection was monitored by viral load and CD4+ T-cell measurements. All control animals were infected and most succumbed to disease. In contrast, protection from superinfection was statistically significant in test monkeys; one animal showed no evidence of superinfection at any time point and the second showed evidence of virus at only one time point over a 6-month observation period. Neither animal showed signs of disease. Perhaps this protective state may serve as a ‘gold-standard’ for HIV-1 vaccine development, as a similar degree of protection against immunodeficiency virus infections in humans would be much desired.
Rhesus macaques, Protective immunity, SHIV, Neutralization, Vaccine
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.