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Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion

The power of mucosal anti-HIV-1 envelope immunoglobulins (Igs) to block virus transmission is underappreciated. We used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. We mucosally instilled recombinant neutralizing monoclonal antibodies (nmAbs) of di...

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Autores principales: Ruprecht, Ruth M., Marasini, Bishal, Thippeshappa, Rajesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963197/
https://www.ncbi.nlm.nih.gov/pubmed/31771162
http://dx.doi.org/10.3390/vaccines7040194
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author Ruprecht, Ruth M.
Marasini, Bishal
Thippeshappa, Rajesh
author_facet Ruprecht, Ruth M.
Marasini, Bishal
Thippeshappa, Rajesh
author_sort Ruprecht, Ruth M.
collection PubMed
description The power of mucosal anti-HIV-1 envelope immunoglobulins (Igs) to block virus transmission is underappreciated. We used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. We mucosally instilled recombinant neutralizing monoclonal antibodies (nmAbs) of different Ig classes in rhesus macaques (RMs) followed by mucosal simian–human immunodeficiency virus (SHIV) challenge. We gave anti-HIV-1 IgM, IgG, and dimeric IgA (dIgA) versions of the same human nmAb, HGN194 that targets the conserved V3 loop crown. Surprisingly, dIgA1 with its wide-open, flat hinge protected 83% of the RMs against intrarectal R5-tropic SHIV-1157ipEL-p challenge, whereas dIgA2, with its narrow hinge, only protected 17% of the animals—despite identical epitope specificities and in vitro neutralization curves of the two dIgA isotypes (Watkins et al., AIDS 2013 27(9):F13-20). These data imply that factors in addition to neutralization determine in vivo protection. We propose that this underlying protective mechanism is immune exclusion, which involves large nmAb/virion aggregates that prevent virus penetration of mucosal barriers. Future studies need to find biomarkers that predict effective immune exclusion in vivo. Vaccine development strategies against HIV-1 and/or other mucosally transmissible pathogens should include induction of strong mucosal Abs of different Ig classes to defend epithelial barriers against pathogen invasion.
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spelling pubmed-69631972020-01-27 Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion Ruprecht, Ruth M. Marasini, Bishal Thippeshappa, Rajesh Vaccines (Basel) Review The power of mucosal anti-HIV-1 envelope immunoglobulins (Igs) to block virus transmission is underappreciated. We used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. We mucosally instilled recombinant neutralizing monoclonal antibodies (nmAbs) of different Ig classes in rhesus macaques (RMs) followed by mucosal simian–human immunodeficiency virus (SHIV) challenge. We gave anti-HIV-1 IgM, IgG, and dimeric IgA (dIgA) versions of the same human nmAb, HGN194 that targets the conserved V3 loop crown. Surprisingly, dIgA1 with its wide-open, flat hinge protected 83% of the RMs against intrarectal R5-tropic SHIV-1157ipEL-p challenge, whereas dIgA2, with its narrow hinge, only protected 17% of the animals—despite identical epitope specificities and in vitro neutralization curves of the two dIgA isotypes (Watkins et al., AIDS 2013 27(9):F13-20). These data imply that factors in addition to neutralization determine in vivo protection. We propose that this underlying protective mechanism is immune exclusion, which involves large nmAb/virion aggregates that prevent virus penetration of mucosal barriers. Future studies need to find biomarkers that predict effective immune exclusion in vivo. Vaccine development strategies against HIV-1 and/or other mucosally transmissible pathogens should include induction of strong mucosal Abs of different Ig classes to defend epithelial barriers against pathogen invasion. MDPI 2019-11-23 /pmc/articles/PMC6963197/ /pubmed/31771162 http://dx.doi.org/10.3390/vaccines7040194 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ruprecht, Ruth M.
Marasini, Bishal
Thippeshappa, Rajesh
Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion
title Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion
title_full Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion
title_fullStr Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion
title_full_unstemmed Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion
title_short Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion
title_sort mucosal antibodies: defending epithelial barriers against hiv-1 invasion
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963197/
https://www.ncbi.nlm.nih.gov/pubmed/31771162
http://dx.doi.org/10.3390/vaccines7040194
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