Neutralizing antibodies are thought to be crucial for HIVa

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

Neutralizing antibodies are thought to be crucial for HIV vaccine protection, but studies in animal models suggest that high antibody concentrations are required. 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 virus. Therefore, animal studies may have provided an overestimate of the levels of antibodies required for protection in humans. The authors investigated whether plasma concentrations of antibody corresponding to relatively modest neutralization titres 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.

This study, as in virtually all similar studies published to date, used viruses matched to the neutralising antibody tested. Thus, it is unclear whether this strategy would protect against a variety of circulating viruses. Nonetheless, it is tantalising to think that this macaque study using low dose viral challenges that better reflect repeated human mucosal exposure to low numbers of virus particles may in some way help us to understand the results of the RV144 Thai vaccine trial in which low risk participants may have been better protected. We await with anticipation further results of that trial over the coming months.