Designed nanofiber immunogens prime antibody responsesto diverse conformations of the HIV-1 fusion peptide

Abstract

Focusing antibody responses towards known neutralizing epitopes is a major strategy for protective immunization. Targeting flexible antigenic regions represents a unique challenge because functional antibodies must be able to bind the epitope of interest in multiple conformations. The fusion peptide (FP) of HIV-1 is a flexible peptide critical to viral entry of host cells for which broadly neutralizing antibodies have been identified. Because elicitation of potent, functional antibodies toward this epitope remains an unmet challenge in HIV-1 vaccination, we introduce a designed immunogen platform capable of raising anti-FP-antibodies with increased conformational tolerance relative to a traditional carrier protein. Antibodies induced by these immunogens bind heterologous FP sequences when elicited in mice and infant non-human primates. This platform shows promise for preclinical development to prime antibody responses toward FP of the HIV-1 envelope and can likely be translated to peptide immunofocusing for other viral pathogens.