Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV
8 affiliations
- 1Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR USA
- 2Vaccine & Gene Therapy Institute, Oregon Health & Science University, Portland, OR USA
- 3California National Primate Research Center, Microbiology and Immunology, University of California, Davis, CA USA
- 4Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 5Present Address: ModeX Therapeutics, Weston, MA USA
- 6Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD USA
- 7Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD USA
- 8Department of Pathology, Microbiology and Immunology, University of California, Davis, CA USA
Abstract
Lack of access to antiretroviral therapy (ART) leads to the transmission of human immunodeficiency virus in ~120,000 children annually, emphasizing the need for new strategies to prevent lifelong infection. Here in an infant rhesus macaque model of peripartum oral infection, we show that broadly neutralizing antibodies directed to the viral envelope protein were insufficient to prevent latent reservoir establishment, independent of daily ART. Blockade of the human immunodeficiency virus co-receptor CCR5 via the antibody leronlimab also failed to prevent reservoir establishment, but it significantly reduced reservoir seeding in lymphoid and gastrointestinal tissues. Following the treatment of infants with viraemia at 72 h post-infection with the combination of broadly neutralizing antibodies, ART and leronlimab, no subsequent evidence of replicating or latent virus and antiviral immunity was observed 1 year after treatment interruption. These findings suggest a synergy between broadly neutralizing antibodies, ART and CCR5 blockade for preventing viral reservoir establishment and offer potential improvements over current therapies for newborns exposed to human immunodeficiency virus.
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BibTeX
@article{sacha2026combination,
title = {{Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV}},
author = {Jonah B. Sacha and Tracy Ordonez and Shilpi Pandey and Gabriela Webb and Philip Barnette and Cleiton Pessoa and Matthew C. Humkey and Jason Reed and Anden Morehead and Jennifer K. Watanabe and Jodie L. Usachenko and Shrivaas Vijayan and Altair Fazio and Heather Sidener and Anne D. Lewis and Gabrielle Pastenkos and Sohita Ojha and Aaron Barber-Axthelm and Bella Swan and Rachele Bochart and John R. Mascola and Amarendra Pegu and Emily J. Fray and Rachael M. Wolters and Janet D. Siliciano and Robert F. Siliciano and Scott G. Hansen and Koen K. A. Van Rompay and Ann J. Hessell and Nancy L. Haigwood},
journal = {Nature Microbiology},
year = {2026},
month = aug,
doi = {10.1038/s41564-026-02444-x},
url = {https://doi.org/10.1038/s41564-026-02444-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV
AU - Jonah B. Sacha
AU - Tracy Ordonez
AU - Shilpi Pandey
AU - Gabriela Webb
AU - Philip Barnette
AU - Cleiton Pessoa
AU - Matthew C. Humkey
AU - Jason Reed
AU - Anden Morehead
AU - Jennifer K. Watanabe
AU - Jodie L. Usachenko
AU - Shrivaas Vijayan
AU - Altair Fazio
AU - Heather Sidener
AU - Anne D. Lewis
AU - Gabrielle Pastenkos
AU - Sohita Ojha
AU - Aaron Barber-Axthelm
AU - Bella Swan
AU - Rachele Bochart
AU - John R. Mascola
AU - Amarendra Pegu
AU - Emily J. Fray
AU - Rachael M. Wolters
AU - Janet D. Siliciano
AU - Robert F. Siliciano
AU - Scott G. Hansen
AU - Koen K. A. Van Rompay
AU - Ann J. Hessell
AU - Nancy L. Haigwood
PY - 2026
DA - 2026/08/10
JO - Nature Microbiology
DO - 10.1038/s41564-026-02444-x
UR - https://doi.org/10.1038/s41564-026-02444-x
AB - Lack of access to antiretroviral therapy (ART) leads to the transmission of human immunodeficiency virus in ~120,000 children annually, emphasizing the need for new strategies to prevent lifelong infection. Here in an infant rhesus macaque model of peripartum oral infection, we show that broadly neutralizing antibodies directed to the viral envelope protein were insufficient to prevent latent reservoir establishment, independent of daily ART. Blockade of the human immunodeficiency virus co-receptor CCR5 via the antibody leronlimab also failed to prevent reservoir establishment, but it significantly reduced reservoir seeding in lymphoid and gastrointestinal tissues. Following the treatment of infants with viraemia at 72 h post-infection with the combination of broadly neutralizing antibodies, ART and leronlimab, no subsequent evidence of replicating or latent virus and antiviral immunity was observed 1 year after treatment interruption. These findings suggest a synergy between broadly neutralizing antibodies, ART and CCR5 blockade for preventing viral reservoir establishment and offer potential improvements over current therapies for newborns exposed to human immunodeficiency virus.
SN - 2058-5276
ER -