Anatomic distribution of intravenously injected IgG takes approximately 1 week to achieve stratum corneum saturation in vaginal tissues

Ann M. Carias, Jeffrey R. Schneider, Patrick Madden, Ramon Lorenzo-Redondo, Mariluz Araınga, Amarendra Pegu, Gianguido C. Cianci, Danijela Maric, Francois Villinger, John R. Mascola, Ronald S. Veazey, Thomas J. Hope*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

L.v. injected Abs have demonstrated protection against simian HIV infection in rhesus macaques, paving the way for the Antibody Mediated Prevention trial in which at-risk individuals for HIV received an i.v. infusion of the HIV broadly neutralizing Ab VRC01. However, the time needed for these Abs to fully distribute and elicit protection at mucosal sites is still unknown. In this study, we interrogate how long it takes for Abs to achieve peak anatomical levels at the vaginal surface following L.v. injection. Fluorescently labeled VRC01 and/or Gamunex-C were L.v. injected into 24 female rhesus macaques (Macaca mulatta) with vaginal tissues and plasma acquired up to 2 wk postinjection. We found that Ab delivery to the vaginal mucosa occurs in two phases. The first phase involves delivery to the submucosa, occurring within 24 h and persisting beyond 1 wk. The second phase is the delivery through the stratified squamous epithelium, needing ~1 wk to saturate the stratum corneum. This study has important implications for the efficacy of immunoprophylaxis targeting pathogens at the mucosa.

Original languageEnglish (US)
Pages (from-to)505-511
Number of pages7
JournalJournal of Immunology
Volume207
Issue number2
DOIs
StatePublished - Jul 15 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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