Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles
Immunofocusing on conserved, subdominant epitopes is critical for vaccines against highly diverse viruses such as HIV-1, influenza, and SARS-CoV-2. The eight-residue N-terminus of the HIV-1 fusion peptide (FP) is one such example of a promising yet small target. We developed new FP immunogens using three alphavirus-like particles (VLPs) and introduced additional glycans to mask shared carrier-specific epitopes. In two independent guinea pig studies, sequential immunization with heterologous carriers enhanced FP-directed antibody titers, which were further improved with glycan engineering. Separately, using diverse FP variants sharing the same N-terminal six amino acids increased neutralizing antibody titers. When combined, these two strategies led to higher FP-directed titers and, after Env trimer boosting, induced FP-directed neutralizing antibodies against multi-clade wild-type HIV-1 in nearly all animals. These findings established the importance of minimizing recurrent off-target epitopes across immunizations and support the engineered VLPs as a promising platform for peptide immunization.
Authors
- Tongqing Zhou (ORCID: https://orcid.org/0000-0002-3935-4637)
- Christian Lee (ORCID: https://orcid.org/0000-0003-2475-9567)
- Chumeng Yang
- Jeffrey C. Boyington (ORCID: https://orcid.org/0000-0003-2610-9445)
- Vedhika Raghunathan (ORCID: https://orcid.org/0000-0002-1484-0524)
- Rui Kong (ORCID: https://orcid.org/0000-0003-1779-5885)
- Lance Wells (ORCID: https://orcid.org/0000-0003-4956-5363)
- Peng Zhao (ORCID: https://orcid.org/0000-0002-9296-5293)
- Hardik K. Nariya (ORCID: https://orcid.org/0000-0003-3601-1927)
- Wei Shi (ORCID: https://orcid.org/0000-0002-0378-8361)
- Seo-Ho Oh
- J Kim
- Tala Azzam (ORCID: https://orcid.org/0000-0001-8739-7861)
- Dedeepya R. Gudipati
- Emily G. McGhee
- Catherine Yang
- John R. Mascola
- Winston Wu
Institutions
- National Institutes of Health (US)
- Emory Healthcare (US)
- Emory University (US)
- University of Georgia (US)
- Emory and Henry College (US)
- Flexion Therapeutics (United States) (US)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1038/s41541-025-01288-6
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Emory University
- Georgia Research Alliance
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Office of Research Infrastructure Programs, National Institutes of Health