Innovating towards an HIV vaccine

Concentrates on developing immunogens and immunization strategies that induce broadly protective antibody responses to HIV. Focus on broadly neutralizing antibodies is strong as they have proven to be protective in robust non-human primate models and because some non-neutralizing antibodies may have protective qualities that might be exploited in vaccine discovery.

GERMLINE-TARGETING: Priming immunogen engineered to broadly activate precursors within a bnAb class; boost immunogens are successively more native-like.

IMMUNOFOCUSING: Immunogen sequence designed to focus responses to one or more particular epitopes.

LINEAGE-BASED DESIGN: Immunogens derived from sequence of Env variants in case studies of bnAb development from natural infection.

For consideration as a clinical candidate, an immunogen will first be expected to meet a number of criteria. We will only pursue development and clinical testing of vaccines that elicit bnAbs under physiological conditions relevant to humans. Detailed analysis and understanding of immune responses in humans will be crucial to iterative vaccine design improvements. Frequencies of polyclonal off-target B cells compete for immunodominance not only during priming but at all stages of sequential vaccination. Polishing trimer immunogens should generally be validated as part of a bnAb-inducing regimen, but if proposed alone must induce nAbs in NHPs.