Characterisation of a Live Salmonella Vaccine Stably Expressing the Mycobacterium Tuberculosis Ag85B-ESAT6 Fusion Protein

Overview

Journal Vaccine

Specialty Allergy & Immunology

Date 2009 Sep 17

PMID 19755145

Citations 11

Authors

Lindsay J Hall

Simon Clare

Derek Pickard

Simon O Clark

Dominic L F Kelly

Moataz Abd El Ghany

Christine Hale

Jes Dietrich

Peter Andersen

Philip D Marsh

Gordon Dougan

Affiliations

Soon will be listed here.

Abstract

A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 T(H)1 response with high antibody titres with a IgG2a-bias and significant IFN-gamma production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6 antigen and adjuvant the IFN-gamma responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.

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