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

Author

Listed:
  • 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
    University of Washington)

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,

Suggested Citation

  • 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 Cole, 2024. "Enhanced and sustained biodistribution of HIV-1 neutralizing antibody VRC01LS in human genital and rectal mucosa," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54580-9
    DOI: 10.1038/s41467-024-54580-9
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    References listed on IDEAS

    as
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