期刊
CRITICAL REVIEWS IN IMMUNOLOGY
卷 30, 期 3, 页码 255-270出版社
BEGELL HOUSE INC
DOI: 10.1615/CritRevImmunol.v30.i3.30
关键词
antigen synthesis; biological containment; delayed attenuation or attenuation; delayed; recombinant vaccines; Salmonella; vaccine
类别
资金
- Bill &Melinda Gates Foundation
- National Institutes of Health
- US Department of Agriculture
- Ellison Medical Foundation
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI060557] Funding Source: NIH RePORTER
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.
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