Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virus

Bacteria are well known to provide heterologous immunity against viral infections through various mechanisms including the induction of innate trained immunity and adaptive cross-reactive immunity. Cross-reactive immunity from bacteria to viruses is responsible for long-term protection and yet its r...

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Main Authors: Andrés Bodas-Pinedo, Esther M. Lafuente, Hector F. Pelaez-Prestel, Alvaro Ras-Carmona, Jose L. Subiza, Pedro A. Reche
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1235053/full
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author Andrés Bodas-Pinedo
Esther M. Lafuente
Hector F. Pelaez-Prestel
Alvaro Ras-Carmona
Jose L. Subiza
Pedro A. Reche
author_facet Andrés Bodas-Pinedo
Esther M. Lafuente
Hector F. Pelaez-Prestel
Alvaro Ras-Carmona
Jose L. Subiza
Pedro A. Reche
author_sort Andrés Bodas-Pinedo
collection DOAJ
description Bacteria are well known to provide heterologous immunity against viral infections through various mechanisms including the induction of innate trained immunity and adaptive cross-reactive immunity. Cross-reactive immunity from bacteria to viruses is responsible for long-term protection and yet its role has been downplayed due the difficulty of determining antigen-specific responses. Here, we carried out a systematic evaluation of the potential cross-reactive immunity from selected bacteria known to induce heterologous immunity against various viruses causing recurrent respiratory infections. The bacteria selected in this work were Bacillus Calmette Guerin and those included in the poly-bacterial preparation MV130: Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Branhamella catarrhalis and Haemophilus influenzae. The virus included influenza A and B viruses, human rhinovirus A, B and C, respiratory syncytial virus A and B and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through BLAST searches, we first identified the shared peptidome space (identity ≥ 80%, in at least 8 residues) between bacteria and viruses, and subsequently predicted T and B cell epitopes within shared peptides. Interestingly, the potential epitope spaces shared between bacteria in MV130 and viruses are non-overlapping. Hence, combining diverse bacteria can enhance cross-reactive immunity. We next analyzed in detail the cross-reactive T and B cell epitopes between MV130 and influenza A virus. We found that MV130 contains numerous cross-reactive T cell epitopes with high population protection coverage and potentially neutralizing B cell epitopes recognizing hemagglutinin and matrix protein 2. These results contribute to explain the immune enhancing properties of MV130 observed in the clinic against respiratory viral infections.
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spelling doaj.art-8ea1921dfead48bca0d14745362bf31c2023-09-08T15:21:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12350531235053Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virusAndrés Bodas-Pinedo0Esther M. Lafuente1Hector F. Pelaez-Prestel2Alvaro Ras-Carmona3Jose L. Subiza4Pedro A. Reche5Children’s Digestive Unit, Institute for Children and Adolescents, Hospital Clinico San Carlos, Madrid, SpainDepartment of Immunology & O2, Faculty of Medicine, University Complutense of Madrid, Ciudad Universitaria, Pza. Ramón y Cajal, Madrid, SpainDepartment of Immunology & O2, Faculty of Medicine, University Complutense of Madrid, Ciudad Universitaria, Pza. Ramón y Cajal, Madrid, SpainDepartment of Immunology & O2, Faculty of Medicine, University Complutense of Madrid, Ciudad Universitaria, Pza. Ramón y Cajal, Madrid, SpainInmunotek, Alcalá de Henares, SpainDepartment of Immunology & O2, Faculty of Medicine, University Complutense of Madrid, Ciudad Universitaria, Pza. Ramón y Cajal, Madrid, SpainBacteria are well known to provide heterologous immunity against viral infections through various mechanisms including the induction of innate trained immunity and adaptive cross-reactive immunity. Cross-reactive immunity from bacteria to viruses is responsible for long-term protection and yet its role has been downplayed due the difficulty of determining antigen-specific responses. Here, we carried out a systematic evaluation of the potential cross-reactive immunity from selected bacteria known to induce heterologous immunity against various viruses causing recurrent respiratory infections. The bacteria selected in this work were Bacillus Calmette Guerin and those included in the poly-bacterial preparation MV130: Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Branhamella catarrhalis and Haemophilus influenzae. The virus included influenza A and B viruses, human rhinovirus A, B and C, respiratory syncytial virus A and B and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through BLAST searches, we first identified the shared peptidome space (identity ≥ 80%, in at least 8 residues) between bacteria and viruses, and subsequently predicted T and B cell epitopes within shared peptides. Interestingly, the potential epitope spaces shared between bacteria in MV130 and viruses are non-overlapping. Hence, combining diverse bacteria can enhance cross-reactive immunity. We next analyzed in detail the cross-reactive T and B cell epitopes between MV130 and influenza A virus. We found that MV130 contains numerous cross-reactive T cell epitopes with high population protection coverage and potentially neutralizing B cell epitopes recognizing hemagglutinin and matrix protein 2. These results contribute to explain the immune enhancing properties of MV130 observed in the clinic against respiratory viral infections.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1235053/fullMV130bacteriarespiratory virusescross-reactivityepitopeinfluenza A virus
spellingShingle Andrés Bodas-Pinedo
Esther M. Lafuente
Hector F. Pelaez-Prestel
Alvaro Ras-Carmona
Jose L. Subiza
Pedro A. Reche
Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virus
Frontiers in Immunology
MV130
bacteria
respiratory viruses
cross-reactivity
epitope
influenza A virus
title Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virus
title_full Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virus
title_fullStr Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virus
title_full_unstemmed Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virus
title_short Combining different bacteria in vaccine formulations enhances the chance for antiviral cross-reactive immunity: a detailed in silico analysis for influenza A virus
title_sort combining different bacteria in vaccine formulations enhances the chance for antiviral cross reactive immunity a detailed in silico analysis for influenza a virus
topic MV130
bacteria
respiratory viruses
cross-reactivity
epitope
influenza A virus
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1235053/full
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