Poster Presentation 9th Australasian Virology Society Meeting 2017

A novel glycan deletion mutation in HIV-1 Env enhances exposure of 4 key broad neutralization epitopes. (#100)

Andy Poumbourios 1 , Hannah AD King 1 2 , David N Harrison 1 , Vani Greetha S Narasimhulu 1 2 , Rob J Center 1 2 , Heidi E Drummer 1 2 3
  1. Virus Entry and Vaccines Laboratory, Burnet Institute, Melbourne , Victoria , Australia
  2. Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC
  3. Department of Microbiology, Monash University, Clayton, VIC

Broadly neutralizing antibodies (bNAbs) have defined the major sites of vulnerability in the gp120-gp41 complex, however, the identification of a vaccine capable of generating bNAbs with the necessary breadth to protect against diverse HIV-1 strains remains elusive. A major obstacle is an immune evasion strategy whereby conserved neutralization epitopes are rendered subdominant due to shielding by glycans or due to competition with higher affinity non-neutralization epitopes for B cell receptors. Our aim is to enhance the expression and potentially the immunodominance of bNAb epitopes in SOSIP gp140 vaccines via a novel mutation in gp120, ΔN, in order to direct the immune response to these epitopes. A preliminary immunogenicity study in guinea pigs revealed that a clade B ΔN SOSIP elicited significantly higher blocking titres relative to WT against 3 of 4 human bNAb epitopes, whose expression was enhanced by ΔN in the SOSIP immunogen. By contrast, ΔN-mediated epitope enhancement and preferential bNAb-like antibody elicitation was not observed with a clade A (BG505) SOSIP immunogen. Thus, the redirection of the immune response to produce bNAb-like specificities by ΔN appears to correlate with its ability to enhance bNAb epitope expression in the SOSIP immunogen. The ΔN mutation is currently being trialled in SOSIPs derived from divergent HIV-1 subtypes.