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

doi:10.4049/jimmunol.2100253

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 journal › Article › peer-review

7 Scopus citations

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)
Pages (from-to)	505-511
Number of pages	7
Journal	Journal of Immunology
Volume	207
Issue number	2
DOIs	https://doi.org/10.4049/jimmunol.2100253
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4049/jimmunol.2100253

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Carias, A. M., Schneider, J. R., Madden, P., Lorenzo-Redondo, R., Araınga, M., Pegu, A., Cianci, G. C., Maric, D., Villinger, F., Mascola, J. R., Veazey, R. S., & Hope, T. J. (2021). Anatomic distribution of intravenously injected IgG takes approximately 1 week to achieve stratum corneum saturation in vaginal tissues. Journal of Immunology, 207(2), 505-511. https://doi.org/10.4049/jimmunol.2100253

@article{079d735f162e4e5f9c61ca27806a09d4,

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

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.",

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

note = "Funding Information: 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.). Funding Information: 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. Publisher Copyright: Copyright {\textcopyright} 2021 by The American Association of Immunologists, Inc.",

year = "2021",

month = jul,

day = "15",

doi = "10.4049/jimmunol.2100253",

language = "English (US)",

volume = "207",

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journal = "Journal of Immunology",

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publisher = "American Association of Immunologists",

number = "2",

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Carias, AM, Schneider, JR, Madden, P, Lorenzo-Redondo, R, Araınga, M, Pegu, A, Cianci, GC, Maric, D, Villinger, F, Mascola, JR, Veazey, RS & Hope, TJ 2021, 'Anatomic distribution of intravenously injected IgG takes approximately 1 week to achieve stratum corneum saturation in vaginal tissues', Journal of Immunology, vol. 207, no. 2, pp. 505-511. https://doi.org/10.4049/jimmunol.2100253

TY - JOUR

T1 - Anatomic distribution of intravenously injected IgG takes approximately 1 week to achieve stratum corneum saturation in vaginal tissues

AU - Carias, Ann M.

AU - Schneider, Jeffrey R.

AU - Madden, Patrick

AU - Lorenzo-Redondo, Ramon

AU - Araınga, Mariluz

AU - Pegu, Amarendra

AU - Cianci, Gianguido C.

AU - Maric, Danijela

AU - Villinger, Francois

AU - Mascola, John R.

AU - Veazey, Ronald S.

AU - Hope, Thomas J.

N1 - Funding Information: 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.). Funding Information: 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. Publisher Copyright: Copyright © 2021 by The American Association of Immunologists, Inc.

PY - 2021/7/15

Y1 - 2021/7/15

N2 - 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.

AB - 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.

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U2 - 10.4049/jimmunol.2100253

DO - 10.4049/jimmunol.2100253

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AN - SCOPUS:85111282309

SN - 0022-1767

VL - 207

SP - 505

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JO - Journal of Immunology

JF - Journal of Immunology

IS - 2

ER -

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

Abstract

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UN SDGs

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