RT Journal Article ID 737fe5d665d99c68 A1 Curtiss III, Roy A1 Xin, Wei A1 Li, Yuhua A1 Kong, Wei A1 Wanda, Soo-Young A1 Gunn, Bronwyn A1 Wang, Shifeng T1 New Technologies in Using Recombinant Attenuated Salmonella Vaccine Vectors JF Critical Reviews™ in Immunology JO CRI YR 2010 FD 2010-04-02 VO 30 IS 3 SP 255 OP 270 K1 antigen synthesis K1 biological containment K1 delayed attenuation or attenuation K1 delayed K1 recombinant vaccines K1 Salmonella K1 vaccine AB 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. PB Begell House LK https://www.dl.begellhouse.com/journals/2ff21abf44b19838,1629d2c3507c27c5,737fe5d665d99c68.html