New technologies in using recombinant attenuated salmonella vaccine vectors

Roy Curtiss, Wei Xin, Yuhua Li, Wei Kong, Soo Young Wanda, Bronwyn Gunn, Shifeng Wang

Research output: Contribution to journalReview article

74 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)255-270
Number of pages16
JournalCritical Reviews in Immunology
Volume30
Issue number3
StatePublished - 2010

Keywords

  • Antigen synthesis
  • Biological containment
  • Delayed
  • Delayed attenuation or attenuation
  • Recombinant vaccines
  • Salmonella
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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