Poster Presentation 50th Lorne Proteins Conference 2025

Epitope Mapping of Elite HIV Neutralisers Uncovers Elevated Proportions of CD4-Binding IgG Antibodies in Blood Plasma (#437)

Anurag Adhikari 1 2 3 , Sauhardra Manandhar 3 , Gopiram (Shulav) Syangtan 3 , Manjula Bhattarai 3 , Purnima Shakya 4 , Lloyd D'Orsogna 5 , Stephanie Gras 1 2 6
  1. Infection and Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, Victoria, Australia, Bundoora, VIC, Nepal
  2. La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia
  3. Department of Infection and Immunology, Kathmandu Research Institute for Biological Sciences, Lalitpur, Bagmati, Nepal
  4. Anti-retroviral Therapy Clinic, Bir Hospital, Kathmandu, Bagmati, Nepal
  5. Pathology & Laboratory Medicine, University of Western Australia, Perth, WA, Australia
  6. Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment (SABE), La Trobe University, Bundoora, VIC, Australia

A key objective in HIV-1 vaccine research is to elicit HIV-1-neutralising antibodies (nAbs) capable of effectively preventing infection and helping clear the presence of the virus. However, little is known about the induction, durability, and epitope targets of these nAbs in individuals with HIV-1 who are virologically suppressed under continuous antiretroviral therapy (uART) since diagnosis.

To investigate the presence of HIV-1 neutralising antibodies, we analyzed plasma IgG-mediated neutralisation against a panel of 12 global HIV-1 pseudoviruses in a cohort of 185 HIV-1+ patients. Our study is unique as we have collected samples from Nepalese HIV patients, which have not been studied.

Preliminary results revealed that 6.5% of patients demonstrated elite neutralising capacity against all pseudovirus variants, with an average neutralisation potency of 25% across the cohort. The frequency of HIV elite controllers in this cohort is higher than what is reported for other cohorts we compared from Germany and Cameroon. The elite HIV neutralizers were further analyzed through polyclonal antibody epitope mapping using a competitive ELISA with HIV-1 recombinant envelope proteins. In 12 elite neutralizers, epitope mapping revealed that plasma antibodies targeting the CD4-binding site (CD4bs) were significantly correlated with neutralization potency. This finding is significant because the CD4bs mediates the initial HIV-host cell entry interaction. As this site is functionally conserved for CD4 receptor interaction, our results indicate that it is likely targeted by antibodies for effective HIV-1 neutralization.

These findings highlight Ab targeting CD4-binding sites, which correlate with neutralization potency, could represent a new target for the development of the HIV-1 vaccine.