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Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses

Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular po...

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Autores principales: Kamuyu, Gathoni, Suen Cheng, Yat, Willcocks, Sam, Kewcharoenwong, Chidchamai, Kiratisin, Pattarachai, Taylor, Peter W., Wren, Brendan W., Lertmemongkolchai, Ganjana, Stabler, Richard A., Brown, Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363311/
https://www.ncbi.nlm.nih.gov/pubmed/34394105
http://dx.doi.org/10.3389/fimmu.2021.705533
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author Kamuyu, Gathoni
Suen Cheng, Yat
Willcocks, Sam
Kewcharoenwong, Chidchamai
Kiratisin, Pattarachai
Taylor, Peter W.
Wren, Brendan W.
Lertmemongkolchai, Ganjana
Stabler, Richard A.
Brown, Jeremy
author_facet Kamuyu, Gathoni
Suen Cheng, Yat
Willcocks, Sam
Kewcharoenwong, Chidchamai
Kiratisin, Pattarachai
Taylor, Peter W.
Wren, Brendan W.
Lertmemongkolchai, Ganjana
Stabler, Richard A.
Brown, Jeremy
author_sort Kamuyu, Gathoni
collection PubMed
description Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular polysaccharides. We have immunized mice with single or multiple A. baumannii strains to induce antibody responses to protein antigens, and then assessed whether these responses provide cross-protection against a collection of genetically diverse clinical A. baumannii isolates. Immunized mice developed antibody responses to multiple protein antigens. Flow cytometry IgG binding assays and immunoblots demonstrated improved recognition of both homologous and heterologous clinical strains in sera from mice immunized with multiple strains compared to a single strain. The capsule partially inhibited bacterial recognition by IgG and the promotion of phagocytosis by human neutrophils. However, after immunization with multiple strains, serum antibodies to protein antigens promoted neutrophil phagocytosis of heterologous A. baumannii strains. In an infection model, mice immunized with multiple strains had lower bacterial counts in the spleen and liver following challenge with a heterologous strain. These data demonstrate that antibodies targeting protein antigens can improve immune recognition and protection against diverse A. baumannii strains, providing support for their use as an antibody therapy.
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spelling pubmed-83633112021-08-14 Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses Kamuyu, Gathoni Suen Cheng, Yat Willcocks, Sam Kewcharoenwong, Chidchamai Kiratisin, Pattarachai Taylor, Peter W. Wren, Brendan W. Lertmemongkolchai, Ganjana Stabler, Richard A. Brown, Jeremy Front Immunol Immunology Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular polysaccharides. We have immunized mice with single or multiple A. baumannii strains to induce antibody responses to protein antigens, and then assessed whether these responses provide cross-protection against a collection of genetically diverse clinical A. baumannii isolates. Immunized mice developed antibody responses to multiple protein antigens. Flow cytometry IgG binding assays and immunoblots demonstrated improved recognition of both homologous and heterologous clinical strains in sera from mice immunized with multiple strains compared to a single strain. The capsule partially inhibited bacterial recognition by IgG and the promotion of phagocytosis by human neutrophils. However, after immunization with multiple strains, serum antibodies to protein antigens promoted neutrophil phagocytosis of heterologous A. baumannii strains. In an infection model, mice immunized with multiple strains had lower bacterial counts in the spleen and liver following challenge with a heterologous strain. These data demonstrate that antibodies targeting protein antigens can improve immune recognition and protection against diverse A. baumannii strains, providing support for their use as an antibody therapy. Frontiers Media S.A. 2021-07-30 /pmc/articles/PMC8363311/ /pubmed/34394105 http://dx.doi.org/10.3389/fimmu.2021.705533 Text en Copyright © 2021 Kamuyu, Suen Cheng, Willcocks, Kewcharoenwong, Kiratisin, Taylor, Wren, Lertmemongkolchai, Stabler and Brown https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Kamuyu, Gathoni
Suen Cheng, Yat
Willcocks, Sam
Kewcharoenwong, Chidchamai
Kiratisin, Pattarachai
Taylor, Peter W.
Wren, Brendan W.
Lertmemongkolchai, Ganjana
Stabler, Richard A.
Brown, Jeremy
Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses
title Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses
title_full Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses
title_fullStr Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses
title_full_unstemmed Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses
title_short Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses
title_sort sequential vaccination with heterologous acinetobacter baumannii strains induces broadly reactive antibody responses
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363311/
https://www.ncbi.nlm.nih.gov/pubmed/34394105
http://dx.doi.org/10.3389/fimmu.2021.705533
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