Advancing an HIV vaccine; advancing vaccinology

Abstract

Of any pathogen, HIV provides perhaps the greatest challenge to successful vaccine development. Nevertheless, progress continued to be made in 2018; new vaccine concepts entered the clinic and new insights were obtained in basic research that will ultimately help to guide rational vaccine design against many’difficult’ pathogens.

Fig. 1 |. A sequential HIV immunization strategy.

Broadly neutralizing antibodies (bnAbs) isolated from infected individuals provide proof of principle that a bnAb-based HIV vaccine is possible. The bnAbs define vaccine targets on native HIV Envelope (Env) trimers (red). Inferred precursors of the bnAbs (often referred to as inferred germline bnAbs) do not generally bind to native trimers, requiring the design of immunogens to activate precursor bnAb B cells (germline-targeting immunogens, for example, eOD-GT8 (yellow)). In order to shepherd the antibody response towards mature bnAbs, a series of immunogens with increasing native trimer-like features are used; these immunogens can be validated by antibodies derived from bnAbs but of lower potency or breadth. Finally, immunization is carried out with native-like trimers such as SOSIP trimers. Immunogen testing uses animal models expressing bnAb precursor B cells (knock-in mice) or human antibody repertoires before moving into the clinic.