Ex vivo evaluation of HIV envelope specific human naive B cells

• Published in: The Journal of immunology (1950) Vol. 196; no. 1_Supplement; pp. 146 - 146.14
• Main Authors: DeBuysscher, Blair L, Steach, Holly R, Stamatatos, Leonidas, Taylor, Justin J.
• Format: Journal Article
• Language: English
• Published: 01.05.2016
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.146.14

Abstract Recent isolation of HIV-1 broadly neutralizing antibodies (bNAbs) has led to vaccine strategies focusing on inducing bNAb responses. Interestingly, not all infected individuals develop bNAbs. Current vaccine candidates regrettable, only induce antibodies that are protective against narrow subsets of strains. This could be because vaccine design is based largely on assumptions that the desired B cells are present in the host, will respond, and are protective. However, recent results suggest that a limited number of B cells respond to vaccination and may require multiple rounds of somatic hypermutation to gain neutralizing breadth. We aim to study pre-vaccination B cell repertoires in hopes of illuminating HIV-1 specific B cell responses to vaccination. Using an HIV envelope (Env)-tetramer enrichment method, we have begun to assess human Env-specific B cells in the blood of HIV-unexposed individuals. This approach allows for careful analysis of the population of naive B cells able to bind to various Env variants, allowing us to compare the germ-line antibody sequences utilized by these cells to the predicted germline sequences of bNAbs. In the course of this work, we have found naive B cells able to cross-react with structurally distinct Envs derived from different clades. Ongoing work is focused on gauging whether naive Env-cross-reactive B cells express antibodies able to broadly neutralize HIV, or can gain this ability after somatic hypermutation.