Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates

Kenneth L. Roland, Steven A. Tinge, Sims K. Kochi, Lawrence J. Thomas, Kevin P. Killeen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Eight Salmonella enterica serovar Paratyphi A strains were screened as candidates to create a live attenuated paratyphoid vaccine. Based on biochemical and phenotypic criteria, four strains, RKS2900, MGN9772, MGN9773 and MGN9779, were selected as progenitors for the construction of ΔphoPQ mutant derivatives. All strains were evaluated in vitro for auxotrophic phenotypes and sensitivity to deoxycholate and polymyxin B. All ΔphoPQ mutants were more sensitive to deoxycholate and polymyxin B than their wild-type progenitors, however MGN10028, MGN10044 and MGN10048, required exogenous purine for optimal growth. Purine requiring strains had acquired point mutations in purB during strain construction. All four mutants were evaluated for reactogenicity and immunogenicity in an oral rabbit model. Three strains were reactogenic in a dose-dependent manner, while one strain, MGN10028, was well-tolerated at all doses administered. All ΔphoPQ strains were immunogenic following a single oral dose. The in vitro profile coupled with the favorable reactogenicity and immunogenicity profiles render MGN10028 a suitable live attenuated Paratyphi A vaccine candidate.

Original languageEnglish (US)
Pages (from-to)3679-3687
Number of pages9
JournalVaccine
Volume28
Issue number21
DOIs
StatePublished - May 7 2010
Externally publishedYes

Fingerprint

Salmonella Paratyphi A
Salmonella paratyphi A
Polymyxin B
Deoxycholic Acid
Typhoid Fever
fever
Vaccines
Typhoid-Paratyphoid Vaccines
immune response
vaccines
Attenuated Vaccines
Point Mutation
deoxycholic acid
Rabbits
polymyxin B
Phenotype
purines
Growth
mutants
mouth

Keywords

  • Live Salmonella vaccine
  • Paratyphi
  • Rabbit model
  • Reactogenicity

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates. / Roland, Kenneth L.; Tinge, Steven A.; Kochi, Sims K.; Thomas, Lawrence J.; Killeen, Kevin P.

In: Vaccine, Vol. 28, No. 21, 07.05.2010, p. 3679-3687.

Research output: Contribution to journalArticle

Roland, Kenneth L. ; Tinge, Steven A. ; Kochi, Sims K. ; Thomas, Lawrence J. ; Killeen, Kevin P. / Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates. In: Vaccine. 2010 ; Vol. 28, No. 21. pp. 3679-3687.
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