Broadly neutralizing antibodies in HIV-1 infection.

An HIV vaccine is desperately needed to prevent new HIV infections worldwide. Approximately 10-30% of HIV infected individuals generate antibodies that are capable of neutralizing a broad range of HIV isolates and these antibodies have been shown to protect against SHIV challenge in Macaque models. Isolation and characterisation of these antibodies has revealed regions of the HIV envelope glycoprotein, gp120/gp41, that are susceptible to antibody binding and re-eliciting these antibodies may be a key step for a successful HIV vaccine. Gp120 is heavily glycosylated with host-derived N-linked glycans and it was previously thought that these glycans shield conserved protein regions from the immune system. However, we have recently shown that many of the most broad and potent HIV neutralizing antibodies bind directly to these glycans highlighting them as potential targets for HIV vaccine design.

Using unique longitudinal patient samples from acutely HIV infected individuals in the SPARTAC study (N Engl J Med 2013;368:207-17) we will investigate the development of HIV broadly neutralizing antibodies (bnAbs) in vivo using in vitro neutralization assays, antigen-specific B cell sorting and antibody cloning, next generation sequencing of antibody genes and viral Envelope single genome amplification. We will determine how the viral Envelope evolution guides and directs bnAb development in these HIV-infected individuals. Ultimately these studies will be used to design immunogens and immunization strategies aimed at re-eliciting these bnAbs through vaccination.