Frontiers in Immunology (Oct 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

  • 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

DOI
https://doi.org/10.3389/fimmu.2023.1246826
Journal volume & issue
Vol. 14

Abstract

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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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