title: New technologies in using recombinant attenuated Salmonella vaccine vectors.
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.
authors.affiliation: The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287-5401, USA. rcurtiss@asu.edu
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Wanda
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Gunn
authors.forename: Shifeng
authors.initials: S
authors.lastname: Wang
mesh_terms: D004274:DNA, Recombinant / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D022562:Salmonella Vaccines / Q000235:genetics* / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics* / Q000276:immunology*
chemical_list: D004274:DNA, Recombinant; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated