Mucosal Delivery of Fusion Proteins with Spores Enhances Protection Against Tuberculosis by Bacillus Calmette-Guérin

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2018 Mar 30

PMID 29593708

Citations 37

Authors

Alastair Copland

Gil R Diogo

Peter Hart

Shane Harris

Andy C Tran

Mathew J Paul

Mahavir Singh

Simon M Cutting

Rajko Reljic

Affiliations

Soon will be listed here.

Abstract

Tuberculosis (TB) is the most deadly infectious disease in existence, and the only available vaccine, (BCG), is almost a century old and poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates a pipeline of diverse novel vaccines. Here, we show that spores can be coated with a fusion protein 1 ("FP1") consisting of (Mtb) antigens Ag85B, ACR, and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose Mtb aerosol challenge model. Mice were primed with subcutaneous BCG, followed by mucosal booster immunizations with Spore-FP1. We show that Spore-FP1 enhanced pulmonary control of Mtb, as evidenced by reduced bacterial burdens in the lungs. This was associated with elevated antigen-specific IgG and IgA titers in the serum and lung mucosal surface, respectively. Spore-FP1 immunization generated superior antigen-specific memory T-cell proliferation in both CD4 and CD8 compartments, alongside bolstered Th1-, Th17-, and Treg-type cytokine production, compared to BCG immunization alone. CD69CD103 tissue resident memory T-cells (Trm) were found within the lung parenchyma after mucosal immunization with Spore-FP1, confirming the advantages of mucosal delivery. Our data show that Spore-FP1 is a promising new TB vaccine that can successfully augment protection and immunogenicity in BCG-primed animals.

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