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Critical Reviews™ in Immunology

Impact factor: 3.889

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v30.i3.30
pages 255-270

New Technologies in Using Recombinant Attenuated Salmonella Vaccine Vectors

Roy Curtiss III
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona
Wei Xin
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona
Yuhua Li
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona
Wei Kong
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona
Soo-Young Wanda
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona
Bronwyn Gunn
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona
Shifeng Wang
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona

ABSTRACT

Recombinant attenuated Salmonella vaccines (RASVs) have been constructed to deliver antigens from other pathogens to induce immunity to those pathogens in vaccinated hosts. The attenuation means should ensure that the vaccine survives following vaccination to colonize lymphoid tissues without causing disease symptoms. This necessitates that attenuation and synthesis of recombinant gene encoded protective antigens do not diminish the ability of orally administered vaccines to survive stresses encountered in the gastrointestinal tract. We have eliminated these problems by using RASVs with regulated delayed expression of attenuation and regulated delayed synthesis of recombinant antigens. These changes result in RASVs that colonize effector lymphoid tissues efficiently to serve as "factories" to synthesize protective antigens that induce higher protective immune responses than achieved when using previously constructed RASVs. We have devised a biological containment system with regulated delayed lysis to preclude RASV persistence in vivo and survival if excreted. Attributes were added to reduce the mild diarrhea sometimes experienced with oral live RASVs and to ensure complete safety in newborns. These collective technologies have been used to develop a novel, low-cost, RASV-synthesizing, multiple-protective Streptococcus pneumoniae antigens that will be safe for newborns/infants and will induce protective immunity to diverse S. pneumoniae serotypes after oral immunization.