Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response
HIV-1 Env glycoprotein (Env) immunogenicity is limited in part by structural instability and extensive glycan shielding and is likely the greatest obstacle to an HIV-1 vaccine. Stabilized Env trimers can elicit serum neutralizing antibodies, but the response is short-lived. Here we use Newcastle Disease Virus-like particle (NDV-VLP) platform to present stabilized versions of HIV-1 Env at high valency and in the context of varied conformational stability, adjuvants, dose, and antigen persistence. Influenza virus hemagglutinin, or SARS-CoV2 Spike-bearing VLPs rapidly induce neutralizing antibodies, in contrast, they were not induced by those bearing Env. A replicating adenovirus type 4 expressing Env rapidly induces autologous neutralizing antibodies. However, durable neutralizing antibodies are induced only when multiple features of a replicating virus infection are combined, with the largest impact from dose and escalating dose. In summary, we show here immunogenicity of HIV-1 Env could be improved by reproducing features of virus infection.
Authors
- P J Roeder (ORCID: https://orcid.org/0009-0000-9604-5235)
- Alyssa A. Pullano (ORCID: https://orcid.org/0000-0002-1170-8667)
- Daniel C. Rogan (ORCID: https://orcid.org/0000-0002-9766-4166)
- Trevor Griesman (ORCID: https://orcid.org/0000-0001-5333-0837)
- Javier Guenaga (ORCID: https://orcid.org/0000-0003-3912-7482)
- Mark R. Harrison (ORCID: https://orcid.org/0009-0003-6976-0120)
- Benjamin I. Leach (ORCID: https://orcid.org/0000-0002-7379-314X)
- Bob C. Lin (ORCID: https://orcid.org/0000-0002-1373-1406)
- Lori McGinnes-Cullen
- Junli Liang (ORCID: https://orcid.org/0000-0001-8062-7230)
- Kenta Matsuda (ORCID: https://orcid.org/0000-0001-7746-3028)
- Tulley Shofner
- Eric Chun‐Pu Chu (ORCID: https://orcid.org/0000-0002-0893-556X)
- Andy Patamawenu
- Mark Connors (ORCID: https://orcid.org/0000-0002-2108-8705)
- Isabel Steinberg (ORCID: https://orcid.org/0009-0004-3173-3634)
- Richard T. Wyatt (ORCID: https://orcid.org/0000-0001-7085-1351)
- Trudy G. Morrison (ORCID: https://orcid.org/0000-0003-2800-7717)
- Gabriel Ozorowski (ORCID: https://orcid.org/0000-0002-9695-8138)
- Iván del Moral-Sánchez (ORCID: https://orcid.org/0000-0002-6356-1484)
- Tyler Stephens
- Mike Castro (ORCID: https://orcid.org/0000-0002-8045-1754)
- Sandeep Narpala (ORCID: https://orcid.org/0000-0002-1447-2709)
- J. J. Webber (ORCID: https://orcid.org/0000-0003-1979-6355)
- Leonid Serebryannyy (ORCID: https://orcid.org/0000-0003-0213-1779)
- Breanna Kim
- Yaroslav Tsybovsky (ORCID: https://orcid.org/0000-0002-2159-5248)
- Ryan N. Lin (ORCID: https://orcid.org/0009-0006-4839-5875)
- Andrew B. Ward (ORCID: https://orcid.org/0000-0001-7153-3769)
- Jessica Pederson
- Jonathan L. Torres (ORCID: https://orcid.org/0000-0003-0137-8497)
- Lyuba Bolkhovitinov
- Ilja Bontjer (ORCID: https://orcid.org/0000-0002-8406-7733)
- Sarah Stuccio (ORCID: https://orcid.org/0000-0003-4758-1984)
- Nathaniel Wright (ORCID: https://orcid.org/0000-0001-7006-4040)
- Rogier W. Sanders (ORCID: https://orcid.org/0000-0002-2324-8573)
- Andy S. Tran (ORCID: https://orcid.org/0009-0004-0508-6015)
- Peter D. Kwong
- Freya van't Veer
- Rachel Roenicke
- Ellison Ober
- Gabrielle Dziubla
- Eleanor Wettstein (ORCID: https://orcid.org/0000-0001-6310-2547)
- Emma Koory
Institutions
- Leidos (United States) (US)
- Scripps Research Institute (US)
- National Institutes of Health (US)
- International AIDS Vaccine Initiative (US)
- University of Massachusetts Chan Medical School (US)
- Frederick National Laboratory for Cancer Research (US)
- National Institute of Allergy and Infectious Diseases (US)
- Amsterdam University Medical Centers (NL)
- University of Amsterdam (NL)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-06-03
- DOI
- https://doi.org/10.1038/s41467-025-60481-2
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases