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Construction and evaluation of a double mutant of Shigella flexneri as a candidate for oral vaccination against shigellosis.

Abstract：

:Based on studies on the genetic and molecular basis of Shigella flexneri invasive properties, we have constructed and evaluated a double mutant of S. flexneri serotype 5 for utilization as a live attenuated oral vaccine against shigellosis. The first mutation, icsA, blocks intracellular spread of bacteria as well as cell-to-cell infection. It affects the capacity of the invasive pathogen to form large abscesses in epithelia. The second mutation, iuc, eliminates production of the siderophore aerobactin thus impairing growth of the bacterium within tissues. This double mutant, SC5700 appeared safe when administered intragastrically to macaque monkeys as three doses (5 x 10(10) c.f.u. each) at weekly intervals. Protection against a challenge by the wild type isolate (M90T) was observed 4 weeks after the last vaccine inoculation. Duration of carriage was considerably reduced as compared to the control group in which all animals had developed severe dysentery. Seroconversion against serotype 5 LPS as well as S. flexneri virulence associated polypeptides was also observed.

journal_name

Vaccine

journal_title

Vaccine

authors

Sansonetti PJ,Arondel J

doi

10.1016/0264-410x(89)90160-6

subject

Has Abstract

pub_date

1989-10-01 00:00:00

pages

443-50

issue

5

eissn

0264-410X

issn

1873-2518

pii

0264-410X(89)90160-6

journal_volume

7

pub_type

杂志文章

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