Enhanced and sustained biodistribution of HIV-1 neutralizing antibody VRC01LS in human genital and rectal mucosa

Maria P. Lemos, Rena D. Astronomo, Yunda Huang, Sandeep Narpala, Madhu Prabhakaran, Philipp Mann, Carmen A. Paez, Yiwen Lu, Gregory J. Mize, Hayley Glantz, Katharine Westerberg, Hunter Colegrove, Kimberly S. Smythe, Minggang Lin, Robert H. Pierce, Julia Hutter, Ian Frank, John R. Mascola, Adrian B. McDermott, Linda-Gail Bekker and M. Juliana McElrath ()
Additional contact information
Maria P. Lemos: Fred Hutchinson Cancer Center
Rena D. Astronomo: Fred Hutchinson Cancer Center
Yunda Huang: Fred Hutchinson Cancer Center
Sandeep Narpala: National Institutes of Health
Madhu Prabhakaran: National Institutes of Health
Philipp Mann: Fred Hutchinson Cancer Center
Carmen A. Paez: Fred Hutchinson Cancer Center
Yiwen Lu: Fred Hutchinson Cancer Center
Gregory J. Mize: Fred Hutchinson Cancer Center
Hayley Glantz: Fred Hutchinson Cancer Center
Katharine Westerberg: Fred Hutchinson Cancer Center
Hunter Colegrove: Fred Hutchinson Cancer Center
Kimberly S. Smythe: Fred Hutchinson Cancer Center
Minggang Lin: Fred Hutchinson Cancer Center
Robert H. Pierce: Fred Hutchinson Cancer Center
Julia Hutter: National Institutes of Health
Ian Frank: University of Pennsylvania
John R. Mascola: ModeX Therapeutics
Adrian B. McDermott: National Institutes of Health
Linda-Gail Bekker: University of Cape Town
M. Juliana McElrath: Fred Hutchinson Cancer Center

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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,

Date: 2024
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DOI: 10.1038/s41467-024-54580-9

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