Purpose of review: Effective vaccine-elicited immunity against HIV-1 infection will likely require broadly neutralizing antibodies to interrupt the fusion-promoting functions of the viral envelope glycoprotein spikes. Efforts in this area have, however, been fraught with challenges. The handful of existing broadly neutralizing monoclonal antibodies has provided information on some of the virus' sites of vulnerability, fueling a decade of structure-informed vaccine design. The fact that very few bnmAbs have been recovered to date illustrates the poor immunogenicity of these epitopes. Recognizing that progress may require more basic information, there has been a notable shift in the field toward identifying new chinks in HIV-1's armor. These efforts are based on the observation that some infected patients develop exceptionally broad serum neutralizing antibodies responses, a better understanding of which would be valuable for vaccine efforts aimed at eliciting similar specificities.
Recent findings: New mapping methodologies are now providing an appreciation of the incidence of specificities similar to the existing known bnmAbs as well as some intriguing insights into novel specificities.
Summary: The new information emerging from mapping efforts should help to sharpen efforts to isolate new bnmAbs and moreover, may provide crucial information for the rational design of novel vaccine candidates.