Construction of recombinant attenuated Salmonella enterica serovar typhimurium vaccine vector strains for safety in newborn and infant mice

Bronwyn M. Gunn, Soo Young Wanda, Dana Burshell, Caihong Wang, Roy Curtiss

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Recombinant bacterial vaccines must be safe, efficacious, and well tolerated, especially when administered to newborns and infants to prevent diseases of early childhood. Many means of attenuation have been shown to render vaccine strains susceptible to host defenses or unable to colonize lymphoid tissue effectively, thus decreasing their immunogenicity. We have constructed recombinant attenuated Salmonella vaccine strains that display high levels of attenuation while retaining the ability to induce high levels of immunogenicity and are well tolerated in high doses when administered to infant mice as young as 24 h old. The strains contain three means of regulated delayed attenuation, as well as a constellation of additional mutations that aid in enhancing safety, regulate antigen expression, and reduce disease symptoms commonly associated with Salmonella infection. The vaccine strains are well tolerated when orally administered to infant mice 24 h old at doses as high as 3.5 × 10 8 CFU.

Original languageEnglish (US)
Pages (from-to)354-362
Number of pages9
JournalClinical and Vaccine Immunology
Volume17
Issue number3
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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