Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques
During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.
Authors
- Mariane B. Melo (ORCID: https://orcid.org/0000-0002-0409-2454)
- David C. Montefiori (ORCID: https://orcid.org/0000-0003-0856-6319)
- Ashley A. Lemnios (ORCID: https://orcid.org/0000-0002-6866-6867)
- Guido Silvestri (ORCID: https://orcid.org/0000-0001-6602-2470)
- Kelli Greene (ORCID: https://orcid.org/0009-0008-6919-9288)
- Julia T. Ngo (ORCID: https://orcid.org/0000-0003-2254-2380)
- Shane Crotty (ORCID: https://orcid.org/0000-0002-6484-6262)
- Daniel Bader (ORCID: https://orcid.org/0000-0001-7731-0494)
- Diane G. Carnathan (ORCID: https://orcid.org/0009-0001-7073-3723)
- Gabriel Ozorowski (ORCID: https://orcid.org/0000-0002-9695-8138)
- Max Crispin (ORCID: https://orcid.org/0000-0002-1072-2694)
- Christopher A. Cottrell (ORCID: https://orcid.org/0000-0002-3364-3083)
- Xiaoying Shen (ORCID: https://orcid.org/0000-0002-8387-3952)
- Katarzyna Kaczmarek Michaels
- Jonathan Hurtado (ORCID: https://orcid.org/0000-0003-4145-7042)
- Sara T. Richey (ORCID: https://orcid.org/0000-0001-7854-1833)
- Payal Pratap (ORCID: https://orcid.org/0000-0002-7170-6866)
- Hongmei Gao (ORCID: https://orcid.org/0000-0002-2468-8589)
- Bryan Briney (ORCID: https://orcid.org/0000-0001-9535-2866)
- Elana Ben‐Akiva (ORCID: https://orcid.org/0000-0003-1085-5902)
- Joel D. Allen (ORCID: https://orcid.org/0000-0003-2547-968X)
- Chiamaka A. Enemuo
- James C. Quinn
- Darrell J. Irvine (ORCID: https://orcid.org/0000-0002-8637-1405)
- Andy S. Tran (ORCID: https://orcid.org/0009-0004-0508-6015)
Institutions
- Scripps Research Institute (US)
- International AIDS Vaccine Initiative (US)
- La Jolla Institute for Immunology (US)
- Howard Hughes Medical Institute (US)
- Emory University (US)
- Duke Medical Center (US)
- University of Southampton (GB)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-08-20
- DOI
- https://doi.org/10.1038/s41541-025-01252-4
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Emory University
- National Institutes of Health
- Yerkes National Primate Research Center, Emory University
- National Institute of Allergy and Infectious Diseases
- Office of Research Infrastructure Programs, National Institutes of Health