Research on broadly neutralizing antibodies (bnAbs) shows that the human immunodeficiency virus (HIV)-research community is still not in a position to elicit a productive neutralizing antibody response by immunization. A large knowledge gap resides at the naïve B-cell level; more precisely on how to engage the precursor B-cell receptor (BCR) in order to efficiently induce proliferation, and how to differentiate B cells to generate such anti-HIV bnAbs.

Lay summary

The main goal of this project is to investigate the naïve B-cell population that can be activated by HIV envelope (Env) proteins by characterizing the responding BCR specificities and diversity in individuals who have not been exposed to the virus. Naïve B-cells that can recognize HIV epitopes exist; otherwise no neutralizing and non-neutralizing antibodies would be developed. But what are the characteristics of this HIV Env-responding cell population? Is it possible to already distinguish naïve B cell of known bnAbs?

Significance of the project
With this project, a system allowing identification of antigen-responding naïve B cells will be created, and the genetic profile of these cells characterized. The created reference database could than be used to interpret Next Generation Sequencing (NGS) data obtained from naturally infected or immunized individuals, will help the understanding of early processes during the generation of the HIV Env-specific antibody response, and will give indications for new vaccines-design.