Frauke Mücksch

In this session, Wilton Williams and Katharine Bar presented studies of broadly neutralizing antibodies as future pathways to a vaccine and a cure. Specifically, the speakers discussed the induction of bNAb responses by engineered HIV-1 immunogens and the application of bNAbs for cure.

Linda-Gail Bekker opened the session by highlighting that “we have to discover an effective preventative vaccine and a scalable cure for those living with HIV”, goals that were subsequently addressed by the speakers Wilton Williams and Katharine Bar. Williams focussed on the HVTN133 trial in which participants were immunized with the HVTN133 immunogen, consisting of gp41 MPER (membrane proximal external region)-peptide liposomes. HVTN133 elicited a polyclonal heterologous antibody response, showing progressive neutralization capacity. This was illustrated by the clonal lineage DH1317 which showed the full range of lineage maturation from MPER precursor Abs to late intermediates/early bNAbs with heterologous HIV-1 neutralization status. Interestingly, lipid binding abilities of DH1317 antibodies correlated with their neutralization potency. Switching to bNAb therapies, while bNAb antiviral activity has been achieved, long-term virus suppression remains a challenge, due to the level of baseline resistance. Bar highlighted the potential of antibodies in HIV cure by discussing several new strategies entailing new and better bNAb combinations, combination immunotherapy in which bNAbs are combined with LRAs and other agents, as well as therapeutic administration of vaccines. In addition, the start of bNAb therapy at ART initiation, prior to establishment of the latent reservoir, was discussed as a promising strategy.

Late intermediates/early bNAbs elicited by a single immunogen are a promising achievement of the HVTN133 trial suggesting potential for greater potency and breadth by repeated immunizations. Reacting to observed adverse events, liposomes will be reformulated without PEG. This session further highlights the potential of antibodies in HIV cure and suggests that the way moving forward are new antibody therapy strategies in which bNAbs are combined with agents such as immune modulators, vaccines, and/or are administered prior to reservoir formation. Taken together, this session gives hope that studying bNAbs might be the solution to achieve both, a vaccine, and a cure.