Enhanced and sustained biodistribution of HIV-1 neutralizing antibody VRC01LS in human genital and rectal mucosa
To prevent sexually-acquired HIV-1 infection by immunoprophylaxis, effective concentrations of broadly neutralizing antibodies are likely needed at mucosal sites of exposure. Here, we examine the biodistribution of monoclonal antibody VRC01 and its extended half-life variant, VRC01LS, in colorectal and genitourinary tracts of healthy adults 1-52 weeks after intravenous infusion. At 1-2 weeks, VRC01LS levels are ~3-4 times higher than VRC01 in serum (p = 0.048), rectal (p = 0.067), vaginal (p = 0.003) and cervical tissues (p = 0.003); these differences increase over time. Both antibodies primarily localize within rectal lamina propria and cervicovaginal stroma, with limited and variable epithelial distribution. Although 8-28% of serum mAb levels reach mucosal tissues, <3% are in seminal and rectal secretions. Elimination half-lives in mucosal tissues are 20-28 days for VRC01 and 51-68 days for VRC01LS. Thus, VRC01LS infusion achieves higher, sustained concentrations in human mucosal tissues than VRC01, supporting the future investigation of potent, long-acting LS-modified antibodies to prevent HIV-1.
Authors
- Adrian B. McDermott (ORCID: https://orcid.org/0000-0003-0616-9117)
- Yunda Huang (ORCID: https://orcid.org/0000-0003-1546-6172)
- Gregory J. Mize (ORCID: https://orcid.org/0000-0003-4680-1893)
- Kimberly S. Smythe (ORCID: https://orcid.org/0000-0002-2329-8298)
- Rena D. Astronomo
- Linda‐Gail Bekker (ORCID: https://orcid.org/0000-0002-0755-4386)
- Maria P. Lemos (ORCID: https://orcid.org/0000-0002-3530-9310)
- Sandeep Narpala
- Yiwen Lu (ORCID: https://orcid.org/0000-0003-4921-7406)
- Ian Frank (ORCID: https://orcid.org/0000-0002-7824-0106)
- Katharine Westerberg
- John R. Mascola (ORCID: https://orcid.org/0000-0002-5293-4695)
- Carmen A. Paez (ORCID: https://orcid.org/0000-0001-8640-6623)
- Philipp Mann (ORCID: https://orcid.org/0000-0001-8130-2032)
- Robert H. Pierce (ORCID: https://orcid.org/0000-0002-2677-144X)
- M. Juliana McElrath (ORCID: https://orcid.org/0000-0003-2276-7117)
- Madhu Prabhakaran (ORCID: https://orcid.org/0000-0002-1981-9054)
- Hayley Glantz (ORCID: https://orcid.org/0000-0002-1017-3488)
- Julia Hütter (ORCID: https://orcid.org/0000-0002-7989-0450)
- Minggang Lin
- Hunter Colegrove (ORCID: https://orcid.org/0000-0002-6660-8460)
Institutions
- National Institutes of Health (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Desmond Tutu HIV Foundation (ZA)
- University of Cape Town (ZA)
- University of Washington (US)
- University of Washington Medical Center (US)
- Fred Hutch Cancer Center (US)
- National Institute of Allergy and Infectious Diseases (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1038/s41467-024-54580-9
- Citations
- 4
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Purdue University
- University of Pennsylvania
- National Institutes of Health