Correlates of broadly neutralizing antibody development

Broadly neutralizing antibodies (bnAbs) are considered a key component of an effective HIV-1 vaccine, but despite intensive efforts, induction of bnAbs by vaccination has thus far not been possible. Potent bnAb activity is rare in natural infection and a deeper understanding of factors that promote or limit bnAb evolution is critical to guide bnAb vaccine development. This review reflects on recent key discoveries on correlates of bnAb development and discusses what further insights are needed to move forward.

An increasing number of parameters have been implicated to influence bnAb development in natural infection. Most recent findings highlight a range of immune factors linked with bnAb evolution. Novel approaches have brought exciting progress in defining signatures of the viral envelope associated with bnAb activity.

Focused efforts of recent years have unraveled a multiply layered process of HIV-1 bnAb development. As it is understood today, bnAb evolution can be triggered and influenced by a range of factors and several different pathways may exist how bnAb induction and maturation can occur. To capitalize on the gained knowledge, future research needs to validate factors to identify independent drivers of bnAb induction to advance vaccine design.