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Frontiers in immunology
2023;14 1263457.

A five-antigen Esx-5a fusion delivered as a prime-boost regimen protects against challenge.

Elena Stylianou, Nawamin Pinpathomrat, Oliver Sampson, Alexandre Richard, Marcellus Korompis, Helen McShane
Author Information
  1. Elena Stylianou: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  2. Nawamin Pinpathomrat: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  3. Oliver Sampson: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  4. Alexandre Richard: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  5. Marcellus Korompis: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  6. Helen McShane: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
PMID: 37869008 DOI: 10.3389/fimmu.2023.1263457

Abstract

The development of tuberculosis (TB) vaccines has been hindered by the complex nature of () and the absence of clearly defined immune markers of protection. While Bacillus Calmette-Guerin (BCG) is currently the only licensed TB vaccine, its effectiveness diminishes in adulthood. In our previous research, we identified that boosting BCG with an intranasally administered chimpanzee adenovirus expressing the PPE15 antigen of (ChAdOx1.PPE15) improved its protection. To enhance the vaccine's efficacy, we combined PPE15 with the other three members of the Esx-5a secretion system and Ag85A into a multi-antigen construct (5Ag). Leveraging the mucosal administration safety of ChAdOx1, we targeted the site of infection to induce localized mucosal responses, while employing modified vaccinia virus (MVA) to boost systemic immune responses. The combination of these antigens resulted in enhanced BCG protection in both the lungs and spleens of vaccinated mice. These findings provide support for advancing ChAdOx1.5Ag and MVA.5Ag to the next stages of vaccine development.

Keywords

BCG Esx mucosa protection subunit tuberculosis vaccines viral-vector

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Grants

  1. /Wellcome Trust

MeSH Term

Mice
Animals
BCG Vaccine
Antigens, Bacterial
Genetic Vectors
Immunization, Secondary
Tuberculosis Vaccines
Vaccinia virus
Mycobacterium bovis

Chemicals

BCG Vaccine
Antigens, Bacterial
Tuberculosis Vaccines
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 3

Word Cloud

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