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 language | English (US) |
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Pages (from-to) | 505-511 |
Number of pages | 7 |
Journal | Journal of Immunology |
Volume | 207 |
Issue number | 2 |
DOIs | |
State | Published - Jul 15 2021 |
Funding
This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health Grants K01OD026571-01 (A.M.C.), K01OD024882-01 (J.R.S.), and HIV Vaccine Research and Design P01AI048240 (T.J.H.) and Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking and Assembly of HIV Grant P50GM082545 (T.J.H.). We acknowledge Constadina Arvanitis and David Kirchenbuchler for assistance with lightsheet microscopy. This work was performed at the North-western University Center for Advanced Microscopy, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. We also acknowledge Patrick Kiser for assistance and expertise with fluorescent-labeling methodologies.
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology