SHIV Infection Protects Against Heterologous Pathogenic SHIV Challenge in Macaques: A Gold-Standard for HIV-1 Vaccine Development?

Abstract

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.

Low-Replicating Viruses and Strong Anti-Viral Immune Response Associated with Prolonged Disease Control in a Superinfected HIV-1 LTNP Elite Controller

“…The observation that neutralizing antibodies are capable of preventing infection in animal models [52] initially suggested that this kind of response might be able to prevent SI in humans. In support of this hypothesis is a study in which the lack of neutralizing antibody response had been associated with a predisposition to SI [53].…”

Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

“…Numerous laboratories have now demonstrated that infection with one immunodeficiency virus (SIV or SHIV) can protect against subsequent infection with another [47–50]. How can this be explained?…”

Murine Monoclonal Antibodies for Antigenic Discrimination of HIV-1 Envelope Proteins

“…Another noteworthy success was with attenuated SIV nef-deletion mutants (16) and with passive transfers of protective antibodies from SIV infected to naive animals (52). Similarly, SHIV infections have been shown to confer protection against heterologous challenges in animal models (17,46), and healthy HIV-1-infected humans have exhibited significant protective immunity against superinfections (12,43). Perhaps individuals once infected with immunodeficiency viruses are protected against heterologous challenges due to the natural evolution of viruses and respective immune responses within the patients (40,42,56).…”