Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates

Tuberculosis remains a major health threat globally and a more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal vaccine candidate is based on the fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed on th...

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Main Authors: Andrew D. White, Andy C. Tran, Laura Sibley, Charlotte Sarfas, Alexandra L. Morrison, Steve Lawrence, Mike Dennis, Simon Clark, Sirine Zadi, Faye Lanni, Emma Rayner, Alastair Copland, Peter Hart, Gil Reynolds Diogo, Matthew J. Paul, Miyoung Kim, Fergus Gleeson, Francisco J. Salguero, Mahavir Singh, Matthias Stehr, Simon M. Cutting, Juan I. Basile, Martin E. Rottenberg, Ann Williams, Sally A. Sharpe, Rajko Reljic
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1246826/full
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author Andrew D. White
Andy C. Tran
Laura Sibley
Charlotte Sarfas
Alexandra L. Morrison
Steve Lawrence
Mike Dennis
Simon Clark
Sirine Zadi
Faye Lanni
Emma Rayner
Alastair Copland
Peter Hart
Gil Reynolds Diogo
Matthew J. Paul
Miyoung Kim
Fergus Gleeson
Francisco J. Salguero
Mahavir Singh
Matthias Stehr
Simon M. Cutting
Simon M. Cutting
Juan I. Basile
Martin E. Rottenberg
Ann Williams
Sally A. Sharpe
Rajko Reljic
author_facet Andrew D. White
Andy C. Tran
Laura Sibley
Charlotte Sarfas
Alexandra L. Morrison
Steve Lawrence
Mike Dennis
Simon Clark
Sirine Zadi
Faye Lanni
Emma Rayner
Alastair Copland
Peter Hart
Gil Reynolds Diogo
Matthew J. Paul
Miyoung Kim
Fergus Gleeson
Francisco J. Salguero
Mahavir Singh
Matthias Stehr
Simon M. Cutting
Simon M. Cutting
Juan I. Basile
Martin E. Rottenberg
Ann Williams
Sally A. Sharpe
Rajko Reljic
author_sort Andrew D. White
collection DOAJ
description Tuberculosis remains a major health threat globally and a more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal vaccine candidate is based on the fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed on the surface of inactivated Bacillus subtilis spores. The candidate conferred significant protection against Mycobacterium. tuberculosis challenge in naïve guinea pigs and markedly improved protection in the lungs and spleens of animals primed with BCG. We then immunized rhesus macaques with BCG intradermally, and subsequently boosted with one intradermal and one aerosol dose of Spore-FP1, prior to challenge with low dose aerosolized M. tuberculosis Erdman strain. Following vaccination, animals did not show any adverse reactions and displayed higher antigen specific cellular and antibody immune responses compared to BCG alone but this did not translate into significant improvement in disease pathology or bacterial burden in the organs.
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spelling doaj.art-5d6971450abd4bfbb64716fb58efad302023-10-10T05:14:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12468261246826Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primatesAndrew D. White0Andy C. Tran1Laura Sibley2Charlotte Sarfas3Alexandra L. Morrison4Steve Lawrence5Mike Dennis6Simon Clark7Sirine Zadi8Faye Lanni9Emma Rayner10Alastair Copland11Peter Hart12Gil Reynolds Diogo13Matthew J. Paul14Miyoung Kim15Fergus Gleeson16Francisco J. Salguero17Mahavir Singh18Matthias Stehr19Simon M. Cutting20Simon M. Cutting21Juan I. Basile22Martin E. Rottenberg23Ann Williams24Sally A. Sharpe25Rajko Reljic26United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomInstitute for Infection and Immunity, St George’s University of London, London, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomInstitute for Infection and Immunity, St George’s University of London, London, United KingdomInstitute for Infection and Immunity, St George’s University of London, London, United KingdomInstitute for Infection and Immunity, St George’s University of London, London, United KingdomInstitute for Infection and Immunity, St George’s University of London, London, United KingdomInstitute for Infection and Immunity, St George’s University of London, London, United KingdomDepartment of Oncology, The Churchill Hospital, Oxford, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomLionex GmbH, Braunschweig, GermanyLionex GmbH, Braunschweig, GermanySchool of Biological Sciences, Royal Holloway University of London, Surrey, United KingdomSporegen Ltd , London Bioscience Innovation Centre, London, United KingdomDepartment of Microbiology, Tumour and Cell Biology and Centre for Tuberculosis Research, Karolinska Institute, Stockholm, SwedenDepartment of Microbiology, Tumour and Cell Biology and Centre for Tuberculosis Research, Karolinska Institute, Stockholm, SwedenUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomUnited Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United KingdomInstitute for Infection and Immunity, St George’s University of London, London, United KingdomTuberculosis remains a major health threat globally and a more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal vaccine candidate is based on the fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed on the surface of inactivated Bacillus subtilis spores. The candidate conferred significant protection against Mycobacterium. tuberculosis challenge in naïve guinea pigs and markedly improved protection in the lungs and spleens of animals primed with BCG. We then immunized rhesus macaques with BCG intradermally, and subsequently boosted with one intradermal and one aerosol dose of Spore-FP1, prior to challenge with low dose aerosolized M. tuberculosis Erdman strain. Following vaccination, animals did not show any adverse reactions and displayed higher antigen specific cellular and antibody immune responses compared to BCG alone but this did not translate into significant improvement in disease pathology or bacterial burden in the organs.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1246826/fulltuberculosisvaccinelungsnon-human primatesaerosol vaccine
spellingShingle Andrew D. White
Andy C. Tran
Laura Sibley
Charlotte Sarfas
Alexandra L. Morrison
Steve Lawrence
Mike Dennis
Simon Clark
Sirine Zadi
Faye Lanni
Emma Rayner
Alastair Copland
Peter Hart
Gil Reynolds Diogo
Matthew J. Paul
Miyoung Kim
Fergus Gleeson
Francisco J. Salguero
Mahavir Singh
Matthias Stehr
Simon M. Cutting
Simon M. Cutting
Juan I. Basile
Martin E. Rottenberg
Ann Williams
Sally A. Sharpe
Rajko Reljic
Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates
Frontiers in Immunology
tuberculosis
vaccine
lungs
non-human primates
aerosol vaccine
title Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates
title_full Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates
title_fullStr Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates
title_full_unstemmed Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates
title_short Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates
title_sort spore fp1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on bcg conferred protection in non human primates
topic tuberculosis
vaccine
lungs
non-human primates
aerosol vaccine
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1246826/full
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