Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis

Stokes, Margaret G. M., Titball, Richard W., Neeson, Brendan N., Galen, James E., Walker, Nicola J., Stagg, Anthony J., Jenner, Dominic C., Thwaite, Joanne E., Nataro, James P., Baillie, Les ORCID: https://orcid.org/0000-0002-8186-223X and Atkins, Helen S. 2007. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infection and Immunity 75 (4) , pp. 1827-1834. 10.1128/IAI.01242-06

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Abstract

Bacillus anthracis is the causative agent of anthrax, a disease that affects wildlife, livestock, and humans. Protection against anthrax is primarily afforded by immunity to the B. anthracis protective antigen (PA), particularly PA domains 4 and 1. To further the development of an orally delivered human vaccine for mass vaccination against anthrax, we produced Salmonella enterica serovar Typhimurium expressing full-length PA, PA domains 1 and 4, or PA domain 4 using codon-optimized PA DNA fused to the S. enterica serovar Typhi ClyA and under the control of the ompC promoter. Oral immunization of A/J mice with Salmonella expressing full-length PA protected five of six mice against a challenge with 105 CFU of aerosolized B. anthracis STI spores, whereas Salmonella expressing PA domains 1 and 4 provided only 25% protection (two of eight mice), and Salmonella expressing PA domain 4 or a Salmonella-only control afforded no measurable protection. However, a purified recombinant fusion protein of domains 1 and 4 provided 100% protection, and purified recombinant 4 provided protection in three of eight immunized mice. Thus, we demonstrate for the first time the efficacy of an oral S. enterica-based vaccine against aerosolized B. anthracis spores.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
ISSN:	00199567
Last Modified:	17 Oct 2022 08:45
URI:	https://orca.cardiff.ac.uk/id/eprint/960

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