Vaccine. 2020 Apr 16; 38(18):3436-3446.
PubMed ID: 32192810
Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity
Lai JI, Eszterhas SK, Brooks SA, Guo C, Zolla-Pazner S, Seaman MS, Bailey-Kellogg C, Griswold KE, Ackerman ME
Antibodies against the HIV-1 V1V2 loops were the only correlate of reduced infection risk in the RV144 vaccine trial, highlighting the V1V2 loops as promising targets for vaccine design. The V1V2 loops are structurally plastic, exhibiting either an α-helix-coil or β-strand conformation. V1V2-specific antibodies may thus recognize distinct conformations, and an antibody's conformational specificity can be an important determinant of breadth and function. Restricting V1V2 conformational plasticity in an immunogen may thus provide control over the conformational specificity and quality of a vaccine-elicited antibody response. Previously, we identified a V1V2 sequence variant (K155M) that results in enhanced recognition by cross-reactive antibodies recognizing the β-strand conformation. Here, we relate V1V2 antigenicity to immunogenicity by comparing the immunogenicity profiles of wildtype and K155M immunogens in two mouse models. In one model, immunization with gp70 V1V2 K155M but not wildtype elicited antibody responses that were cross-reactive to a panel of heterologous gp120 and gp140 antigens. In a second model, we compared the effect of K155M on immunogenicity in the context of gp70 V1V2, gD V1V2 and gp120, examining the effects of scaffold, epitope-focusing and immunization regimen. K155M variants, especially in the context of a gp120 immunogen, resulted in more robust, durable and cross-reactive antibody responses than wildtype immunogens. Restriction of the β-stranded V1V2 conformation in K155M immunogens may thus be associated with the induction of cross-reactive antibody responses thought to be required of a protective HIV-1 vaccine.
With the publicly available data in the CAVD DataSpace we can
Learn about studies, products, assays, antibodies, and publications,
Find subjects with common characteristics,
Plot assay results across studies and years of research, and
Compare monoclonal antibodies and their neutralization curves.
Data are also accessible via DataSpaceR, our R API.
Sign in to see full information about this publication and to download study data when available.