Antibodies from another CAPRISA participant provide insights for vaccine science
Two papers published in December 2018 by the team at the National Institute of Communicable Diseases (NICD) describe monoclonal antibodies (mAbs) isolated from another participant in the CAPRISA 002 cohort. This time, its CAP228 who developed a non-neutralizing antibody response to the V2 region, similar to what was seen in the moderately effective RV144 vaccine trial.
The first paper by Kurt Wibmer, in Nature Communications, reports on the cocrystal structures of the CAP228 antibodies complexed with scaffolded V1V2 proteins. These antibodies recognize the same helix-coil V2 conformation as RV144 antibody CH58, identifying an alternative conformation of V1V2. This α-helical form of V1V2 displays highly exposed α4β7-binding sites, potentially providing a functional role for non-native envelope on virion or infected cell surfaces through blocking interactions with integrins.
The second paper published in Cell Reports by Charmaine van Eeden and Kurt Wibmer details the biological and genetic properties of the CAP228 mAbs. These mAbs resemble vaccine-elicited mAbs but make use of a novel antibody light chain and show broader ADCC activity against globally relevant V2 immunotypes.
This additional light chain increases the repertoire of B cells able to respond to RV144 V2 immunogens and opens up the possibility that vaccines based on RV144 (as is currently being tested in HVTN 702) may show higher levels of efficacy in South Africa.
For further reading see:
Wibmer CK et al. Nat Commun. 2018; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203816/
van Eeden C et al. Cell Reports 2018; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342559/
· V2-specific antibodies from HIV infection that resemblevaccine-elicited antibodies
· Use of a different antibody light chain with a different V2K169-binding motif
· Show broad ADCC activity against globally relevant V2 immunotypes
· Increases the repertoire of B cells able to respond to RV144V2 immunogens