HIV broadly neutralizing antibodies: VRC01 and beyond

Abstract

Developing an effective prophylaxis HIV-1 vaccine is likely to require the elicitation of broadly neutralizing antibodies (bnAbs). As the HIV-1 envelope (Env) glycoprotein - the sole target of bnAbs - has evolved multiple mechanisms to evade antibody neutralization, the processes for bnAb generation are highly selective and time-consuming. Benefiting from antibody isolation technologies of single B cell culturing and direct single B cell sorting and cloning, a new generation of monoclonal bnAbs has been isolated since 2009, exhibiting remarkable breadths and potencies, thus breaking through a nearly 20-year-long limit of four monoclonal bnAbs with moderate breadth and potency. The discovery of a long list of monoclonal bnAbs has provided in-depth understanding of the sites of vulnerability on the HIV-1 Env and the complexity of human B cell immunology to generate such responses, thus presenting both guidance and challenges to move the Env immunogen design effort forward.