Construction and characterization of a Vi-positive variant of the Salmonella typhi live oral vaccine strain Ty21a.

Abstract:

:The viaB locus coding for the Vi antigen of Salmonella typhi Ty2 was cloned on a 40.6-kilobase fragment into the cosmid vector pHC79. The live, oral, attenuated Vi-negative S. typhi Ty21a vaccine strain was transformed with the recombinant cosmid encoding the viaB locus. Homologous recombination of the viaB locus into the chromosome of S. typhi Ty21a was induced by UV irradiation, and Vi-positive recombinants were selected in the presence of D-cycloserine. One such isolate, termed WR4103, contained no plasmids or the attendant antibiotic resistance markers and expressed the Vi antigen stably. Vi antigen extracted from WR4103 was immunologically indistinguishable from Vi antigen purified from S. typhi Ty2. The only detectable difference between Ty21a and WR4103 was in the production of Vi antigen. The mean lethal doses of Ty21a and WR4103 for mice were nearly identical. Immunization of mice with WR4103 engendered a Vi antibody response and afforded complete protection against fatal infection with virulent S. typhi Ty2. Thus, S. typhi WR4103 may serve as an improved oral vaccine for protection against typhoid fever.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Cryz SJ Jr,Fürer E,Baron LS,Noon KF,Rubin FA,Kopecko DJ

doi

10.1128/IAI.57.12.3863-3868.1989

subject

Has Abstract

pub_date

1989-12-01 00:00:00

pages

3863-8

issue

12

eissn

0019-9567

issn

1098-5522

journal_volume

57

pub_type

杂志文章