A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions
To eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple broadly neutralizing antibody (bNAb) combination comprising of 3BNC117, PGDM1400 and PGT151 that mediates robust in vitro neutralization and non-neutralizing effector functions against a cross-clade panel of simian human immunodeficiency viruses (SHIVs). In this study, we evaluated the safety, pharmacokinetics, and antiviral potency of this bNAb combination in infant rhesus macaques (RMs). We demonstrate that subcutaneous infusion of the triple bNAb regimen was well tolerated in pediatric monkeys and resulted in durable systemic and mucosal distribution. Plasma obtained from passively-immunized RMs demonstrated potent HIV-neutralizing and Fc-mediated antiviral effector functions. Finally, using the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker threshold of >200, which was recently identified as a surrogate endpoint for evaluation of the preventative efficacy of bNAbs against mucosal viral acquisition in human clinical trials, we demonstrated that our regimen has PT80>200 against a large panel of plasma and breast milk-derived HIV strains and cross-clade SHIV variants. This data will guide the development of combination bNAbs for eliminating vertical HIV transmission and for achieving ART-free viral suppression among children living with HIV.
Authors
- Kathleen Engelman (ORCID: https://orcid.org/0000-0002-1233-7335)
- Guido Silvestri (ORCID: https://orcid.org/0000-0001-6602-2470)
- Cliburn Chan (ORCID: https://orcid.org/0000-0001-5901-6806)
- Genevieve G. Fouda (ORCID: https://orcid.org/0000-0002-0960-1019)
- Julia T. Ngo (ORCID: https://orcid.org/0000-0003-2254-2380)
- Stella J. Berendam (ORCID: https://orcid.org/0000-0001-9622-2238)
- Janice McCarthy (ORCID: https://orcid.org/0000-0001-7351-6276)
- Maria Dennis (ORCID: https://orcid.org/0000-0003-0833-2635)
- Rama Rao Amara (ORCID: https://orcid.org/0000-0002-6309-6797)
- Ria Goswami (ORCID: https://orcid.org/0000-0002-4574-5431)
- Diane G. Carnathan (ORCID: https://orcid.org/0009-0001-7073-3723)
- Guido Ferrari (ORCID: https://orcid.org/0000-0001-7747-3349)
- Sherry Stanfield-Oakley (ORCID: https://orcid.org/0000-0002-6347-1956)
- Sallie R. Permar (ORCID: https://orcid.org/0000-0003-1438-4554)
- Sedem Dankwa (ORCID: https://orcid.org/0000-0003-1121-3936)
- Bryan T. Mayer (ORCID: https://orcid.org/0000-0003-2258-5276)
- Carolyn Weinbaum
- Diogo M. Magnani (ORCID: https://orcid.org/0000-0002-1773-2406)
- Ann Chahroudi (ORCID: https://orcid.org/0000-0001-7479-9546)
- Chiamaka A. Enemuo
- Elena E. Giorgi (ORCID: https://orcid.org/0000-0003-2968-1033)
- Ioanna Pahountis
- Christian Binuya
- Ashley Garza
- Kenneth Vuong
- Christina Kosman
Institutions
- Emory University (US)
- University of Massachusetts Chan Medical School (US)
- Duke University (US)
- Cornell University (US)
- Fred Hutch Cancer Center (US)
- Children's Healthcare of Atlanta (US)
- Weill Cornell Medicine (US)
Publication Details
- Journal
- PLoS ONE
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1371/journal.pone.0312411
- Citations
- 1
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.29
Funders
- University of Pennsylvania
- National Institutes of Health
- NIH Office of the Director
- National Institute of Allergy and Infectious Diseases
- Office of Research Infrastructure Programs, National Institutes of Health