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

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

doi:10.3389/fimmu.2023.1246826

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

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 StehrSimon M. Cutting, Juan I. Basile, Martin E. Rottenberg, Ann Williams, Sally A. Sharpe^*, Rajko Reljic^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

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.

Original language	English
Article number	1246826
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1246826
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 White, Tran, Sibley, Sarfas, Morrison, Lawrence, Dennis, Clark, Zadi, Lanni, Rayner, Copland, Hart, Diogo, Paul, Kim, Gleeson, Salguero, Singh, Stehr, Cutting, Basile, Rottenberg, Williams, Sharpe and Reljic.

Keywords

aerosol vaccine
lungs
non-human primates
tuberculosis
vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fimmu.2023.1246826

Cite this

White, A. D., Tran, A. C., Sibley, L., Sarfas, C., Morrison, A. L., Lawrence, S., Dennis, M., Clark, S., Zadi, S., Lanni, F., Rayner, E., Copland, A., Hart, P., Diogo, G. R., Paul, M. J., Kim, M., Gleeson, F., Salguero, F. J., Singh, M., ... Reljic, R. (2023). 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, 14, Article 1246826. https://doi.org/10.3389/fimmu.2023.1246826

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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",

abstract = "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 na{\"i}ve 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.",

keywords = "aerosol vaccine, lungs, non-human primates, tuberculosis, vaccine",

author = "White, {Andrew D.} and Tran, {Andy C.} and Laura Sibley and Charlotte Sarfas and Morrison, {Alexandra L.} and Steve Lawrence and Mike Dennis and Simon Clark and Sirine Zadi and Faye Lanni and Emma Rayner and Alastair Copland and Peter Hart and Diogo, {Gil Reynolds} and Paul, {Matthew J.} and Miyoung Kim and Fergus Gleeson and Salguero, {Francisco J.} and Mahavir Singh and Matthias Stehr and Cutting, {Simon M.} and Basile, {Juan I.} and Rottenberg, {Martin E.} and Ann Williams and Sharpe, {Sally A.} and Rajko Reljic",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 White, Tran, Sibley, Sarfas, Morrison, Lawrence, Dennis, Clark, Zadi, Lanni, Rayner, Copland, Hart, Diogo, Paul, Kim, Gleeson, Salguero, Singh, Stehr, Cutting, Basile, Rottenberg, Williams, Sharpe and Reljic.",

year = "2023",

doi = "10.3389/fimmu.2023.1246826",

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White, AD, Tran, AC, Sibley, L, Sarfas, C, Morrison, AL, Lawrence, S, Dennis, M , Clark, S, Zadi, S, Lanni, F, Rayner, E, Copland, A, Hart, P, Diogo, GR, Paul, MJ, Kim, M, Gleeson, F, Salguero, FJ, Singh, M, Stehr, M, Cutting, SM, Basile, JI, Rottenberg, ME, Williams, A, Sharpe, SA & Reljic, R 2023, '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, vol. 14, 1246826. https://doi.org/10.3389/fimmu.2023.1246826

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AU - White, Andrew D.

AU - Tran, Andy C.

AU - Sibley, Laura

AU - Sarfas, Charlotte

AU - Morrison, Alexandra L.

AU - Lawrence, Steve

AU - Dennis, Mike

AU - Clark, Simon

AU - Zadi, Sirine

AU - Lanni, Faye

AU - Rayner, Emma

AU - Copland, Alastair

AU - Hart, Peter

AU - Diogo, Gil Reynolds

AU - Paul, Matthew J.

AU - Kim, Miyoung

AU - Gleeson, Fergus

AU - Salguero, Francisco J.

AU - Singh, Mahavir

AU - Stehr, Matthias

AU - Cutting, Simon M.

AU - Basile, Juan I.

AU - Rottenberg, Martin E.

AU - Williams, Ann

AU - Sharpe, Sally A.

AU - Reljic, Rajko

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N2 - 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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KW - lungs

KW - non-human primates

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SN - 1664-3224

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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