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Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection

Acinetobacter baumannii is a human bacterial pathogen of increasing concern in clinical settings due to the emergence of antibiotic resistant strains and the lack of effective therapeutics. Researchers have been exploring new treatment options such as novel drug candidates and vaccines to prevent se...

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Autores principales: Chaudhuri, Somshukla, Rasooli, Iraj, Oskouei, Ramin Hatefi, Pishgahi, Mahdi, Jahangir, Abolfazl, Andisi, Vahid Farshchi, Schryvers, Anthony B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420935/
https://www.ncbi.nlm.nih.gov/pubmed/36045685
http://dx.doi.org/10.3389/fimmu.2022.933445
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author Chaudhuri, Somshukla
Rasooli, Iraj
Oskouei, Ramin Hatefi
Pishgahi, Mahdi
Jahangir, Abolfazl
Andisi, Vahid Farshchi
Schryvers, Anthony B.
author_facet Chaudhuri, Somshukla
Rasooli, Iraj
Oskouei, Ramin Hatefi
Pishgahi, Mahdi
Jahangir, Abolfazl
Andisi, Vahid Farshchi
Schryvers, Anthony B.
author_sort Chaudhuri, Somshukla
collection PubMed
description Acinetobacter baumannii is a human bacterial pathogen of increasing concern in clinical settings due to the emergence of antibiotic resistant strains and the lack of effective therapeutics. Researchers have been exploring new treatment options such as novel drug candidates and vaccines to prevent severe infections and mortality. Bacterial surface antigens that are essential to A. baumannii for acquiring micronutrients (e.g. iron, zinc) from nutrient restricted environments are being considered as targets for vaccines or immunotherapy due to their crucial role for growth and pathogenesis in the human host. BauA, the outer membrane receptor for the siderophore acinetobactin was targeted for vaccine development in this study. Due to challenges in the commercial production of membrane proteins for vaccines, a novel hybrid antigen method developed by our group was used. Exposed loops of BauA were selected and displayed on a foreign scaffold to generate novel hybrid antigens designed to elicit an immune response against the native BauA protein. The potential epitopes were incorporated into a scaffold derived from the C-lobe of Neisseria meningitidis transferrin binding protein B (TbpB), named the loopless C-lobe (LCL). Hybrid proteins displaying three selected loops (5, 7 and 8) individually or in combination were designed and produced and evaluated in an A. baumannii murine sepsis model as vaccine antigens. Immunization with the recombinant BauA protein protected 100% of the mice while immunization with hybrid antigens displaying individual loops achieved between 50 and 100% protection. The LCL scaffold did not induce a protective immune response, enabling us to attribute the observed protection elicited by the hybrid antigens to the displayed loops. Notably, the mice immunized with the hybrid antigen displaying loop 7 were completely protected from infection. Taken together, these results suggest that our hybrid antigen approach is a viable method for generating novel vaccine antigens that target membrane surface proteins necessary for bacterial growth and pathogenesis and the loop 7 hybrid antigen can be a foundation for approaches to combat A. baumannii infections.
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spelling pubmed-94209352022-08-30 Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection Chaudhuri, Somshukla Rasooli, Iraj Oskouei, Ramin Hatefi Pishgahi, Mahdi Jahangir, Abolfazl Andisi, Vahid Farshchi Schryvers, Anthony B. Front Immunol Immunology Acinetobacter baumannii is a human bacterial pathogen of increasing concern in clinical settings due to the emergence of antibiotic resistant strains and the lack of effective therapeutics. Researchers have been exploring new treatment options such as novel drug candidates and vaccines to prevent severe infections and mortality. Bacterial surface antigens that are essential to A. baumannii for acquiring micronutrients (e.g. iron, zinc) from nutrient restricted environments are being considered as targets for vaccines or immunotherapy due to their crucial role for growth and pathogenesis in the human host. BauA, the outer membrane receptor for the siderophore acinetobactin was targeted for vaccine development in this study. Due to challenges in the commercial production of membrane proteins for vaccines, a novel hybrid antigen method developed by our group was used. Exposed loops of BauA were selected and displayed on a foreign scaffold to generate novel hybrid antigens designed to elicit an immune response against the native BauA protein. The potential epitopes were incorporated into a scaffold derived from the C-lobe of Neisseria meningitidis transferrin binding protein B (TbpB), named the loopless C-lobe (LCL). Hybrid proteins displaying three selected loops (5, 7 and 8) individually or in combination were designed and produced and evaluated in an A. baumannii murine sepsis model as vaccine antigens. Immunization with the recombinant BauA protein protected 100% of the mice while immunization with hybrid antigens displaying individual loops achieved between 50 and 100% protection. The LCL scaffold did not induce a protective immune response, enabling us to attribute the observed protection elicited by the hybrid antigens to the displayed loops. Notably, the mice immunized with the hybrid antigen displaying loop 7 were completely protected from infection. Taken together, these results suggest that our hybrid antigen approach is a viable method for generating novel vaccine antigens that target membrane surface proteins necessary for bacterial growth and pathogenesis and the loop 7 hybrid antigen can be a foundation for approaches to combat A. baumannii infections. Frontiers Media S.A. 2022-08-15 /pmc/articles/PMC9420935/ /pubmed/36045685 http://dx.doi.org/10.3389/fimmu.2022.933445 Text en Copyright © 2022 Chaudhuri, Rasooli, Oskouei, Pishgahi, Jahangir, Andisi and Schryvers 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
Chaudhuri, Somshukla
Rasooli, Iraj
Oskouei, Ramin Hatefi
Pishgahi, Mahdi
Jahangir, Abolfazl
Andisi, Vahid Farshchi
Schryvers, Anthony B.
Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection
title Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection
title_full Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection
title_fullStr Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection
title_full_unstemmed Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection
title_short Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection
title_sort hybrid antigens expressing surface loops of baua from acinetobacter baumannii are capable of inducing protection against infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420935/
https://www.ncbi.nlm.nih.gov/pubmed/36045685
http://dx.doi.org/10.3389/fimmu.2022.933445
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