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

Immunology

Juan I. Basile¹  Martin E. Rottenberg¹  Fergus Gleeson²  Miyoung Kim³  Alastair Copland³  Peter Hart³  Andy C. Tran³  Matthew J. Paul³  Rajko Reljic³  Gil Reynolds Diogo³  Matthias Stehr⁴  Mahavir Singh⁴  Simon M. Cutting⁵  Charlotte Sarfas⁶  Mike Dennis⁶  Laura Sibley⁶  Sirine Zadi⁶  Alexandra L. Morrison⁶  Faye Lanni⁶  Francisco J. Salguero⁶  Steve Lawrence⁶  Andrew D. White⁶  Ann Williams⁶  Sally A. Sharpe⁶  Simon Clark⁶  Emma Rayner⁶ 

[1] Department of Microbiology, Tumour and Cell Biology and Centre for Tuberculosis Research, Karolinska Institute, Stockholm, Sweden;Department of Oncology, The Churchill Hospital, Oxford, United Kingdom;Institute for Infection and Immunity, St George’s University of London, London, United Kingdom;Lionex GmbH, Braunschweig, Germany;School of Biological Sciences, Royal Holloway University of London, Surrey, United Kingdom;Sporegen Ltd , London Bioscience Innovation Centre, London, United Kingdom;United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom;

关键词: tuberculosis;    vaccine;    lungs;    non-human primates;    aerosol vaccine;   

DOI  :  10.3389/fimmu.2023.1246826

 received in 2023-06-24, accepted in 2023-09-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
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