Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques

Abstract

Studies in macaques have shown that neutralizing antibodies can offer robust protection from infection with a simian counterpart of HIV, yet these studies have also suggested that high concentrations of antibodies are required for efficient protection. Unfortunately, it's not generally thought to be feasible to elicit such high neutralizing antibody titers by vaccination. Dennis Burton and his colleagues now show that lower concentrations of antibodies can offer protection to macaques if a repeated low-dose challenge model is used—a model that may better recapitulate the acquisition of infection in humans. Neutralizing antibodies are thought to be crucial for HIV vaccine protection, but studies in animal models suggest that high antibody concentrations are required1. This is a major potential hurdle for vaccine design. However, these studies typically apply a large virus inoculum to ensure infection in control animals in single-challenge experiments. In contrast, most human infection via sexual encounter probably involves repeated exposures to much lower doses of virus2,3,4. Therefore, animal studies may have provided an overestimate of the levels of antibodies required for protection in humans. We investigated whether plasma concentrations of antibody corresponding to relatively modest neutralization titers in vitro could protect macaques from repeated intravaginal exposure to low doses of a simian immunodeficiency virus–HIV chimera (SHIV) that uses the CC chemokine receptor 5 (CCR5) co-receptor. An effector function–deficient variant of the neutralizing antibody was also included. The results show that a substantially larger number of challenges is required to infect macaques treated with neutralizing antibody than control antibody–treated macaques, and support the notion that effector function may contribute to antibody protection. Overall, the results imply that lower amounts of antibody than previously considered protective may provide benefit in the context of typical human exposure to HIV-1.