HIV-1 Envelope gp41 Broadly Neutralizing Antibodies: Hurdles for Vaccine Development

A primary correlate of protection for most effective viral vaccines is induction of antibodies with potent virus neutralization [1]. HIV-1 differs from other viruses for which successful vaccines have been made, because as a highly mutable, integrating retrovirus, it is resistant to both immune responses and antiretroviral therapy upon establishment of a latently infected CD4+ T-cell pool [2]. Thus, to prevent infection, an HIV-1 vaccine must induce protective immunity that is active during transmission [3]. Broadly neutralizing antibodies (bnAbs) are targeted to conserved regions of the HIV-1 envelope (Env) and neutralize a broad spectrum of HIV-1 quasi-species [4]. When passively infused in rhesus macaques [5]–[8] or transduced in humanized mice [9] preceding challenge, bnAbs robustly prevent infection, suggesting they can protect if present during transmission. However, bnAbs are made in a minority of HIV-1–infected individuals years after infection and cannot be elicited by current immunization regimens [3]. Thus, identifying impediments to bnAb induction to devise better immunization strategies is a central goal for HIV-1 vaccine development.