Triggering rare HIV antibodies by vaccination

Description Clinical trial shows that an HIV vaccine can elicit rare antibodies, but there is more to do An HIV vaccine is urgent: A recent UNAIDS report entitled “In Danger” showed that in 2021, one adolescent girl or young woman became infected with HIV every 2 min, especially in sub-Saharan Africa (1). A vaccine will likely need to elicit broadly neutralizing antibodies (bnAbs), which are able to recognize globally diverse HIV strains and can prevent HIV infection (2). However, triggering bnAbs by vaccination has proven impossible so far. A key challenge is that bnAbs rarely develop, even during infection. Furthermore, bnAb precursors (or germlines) are uncommon in human immunological repertoires. Devising vaccines specifically aimed at recruiting these rare precursors, an approach referred to as “germline targeting,” has driven major immunological advances with broad applicability for other pathogens. On page 964 of this issue, Leggat et al. (3) provide clinical proof of concept for the germline-targeting approach for HIV vaccination and detailed immunological insights upon which future vaccine trials can be designed.