Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates.

Eight Salmonella enterica serovar Paratyphi A strains were screened as candidates to create a live attenuated paratyphoid vaccine. Based on biochemical and phenotypic criteria, four strains, RKS2900, MGN9772, MGN9773 and MGN9779, were selected as progenitors for the construction of DeltaphoPQ mutant derivatives. All strains were evaluated in vitro for auxotrophic phenotypes and sensitivity to deoxycholate and polymyxin B.

Salmonella enterica serovar typhimurium strains with regulated delayed attenuation in vivo.

Recombinant bacterial vaccines must be fully attenuated for animal or human hosts to avoid inducing disease symptoms while exhibiting a high degree of immunogenicity. Unfortunately, many well-studied means for attenuating Salmonella render strains more susceptible to host defense stresses encountered following oral vaccination than wild-type virulent strains and/or impair their ability to effectively colonize the gut-associated and internal lymphoid tissues. This thus impairs the ability of recombinant vaccines to serve as factories to produce recombinant antigens to induce the desired protective immunity.

Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment.

We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using Salmonella enterica serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts.

Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is the leading cause of traveler's diarrhea. The heat-labile (LT) and heat-stable (ST) toxins mediate ETEC induced diarrhea. ETEC strains may express LT, ST, or both LT and ST, with LT-expressing strains accounting for approximately 50-60% of ETEC-related traveler's diarrhea.

Recent advances in the development of live, attenuated bacterial vectors.

Over the last quarter century, scientific advances have created new tools and technologies to improve the safety and efficacy of vaccines. These improvements are spurred by social and commercial needs to enhance existing vaccines or to create new ones against an expanding spectrum of diseases. Vaccines based on live, attenuated, pathogenic bacteria were originally developed to prevent infection by homologous pathogens.