RRC ID |
3036
|
Author |
Suzuki T, Yoshikawa Y, Ashida H, Iwai H, Toyotome T, Matsui H, Sasakawa C.
|
Title |
High vaccine efficacy against shigellosis of recombinant noninvasive Shigella mutant that expresses Yersinia invasin.
|
Journal |
J Immunol
|
Abstract |
Live attenuated Shigella vaccines elicit protective immune responses, but involve a potential risk of inducing a strong inflammatory reaction. The bacterial invasiveness that is crucial for Ag delivery causes inflammatory destruction of infected epithelial cells and proinflammatory cell death of infected macrophages. In this study, the noninvasive Shigella mutant DeltaipaB was equipped with Yersinia invasin protein, which has been shown to mediate bacterial invasion and targeting to M cells located in follicle-associated epithelium. Invasin-expressing DeltaipaB (DeltaipaB/inv) was internalized into epithelial cells and retained in the intraphagosomal space. DeltaipaB/inv did not induce necrotic cell death of infected macrophages nor cause symptomatic damage after intranasal vaccination of mice. DeltaipaB/inv was safer and more effective than the conventional live vaccine, DeltavirG. Infection by DeltaipaB/inv caused polymorphonuclear neutrophil infiltration in the lung, but did not induce production of large amounts of proinflammatory cytokines. We concluded that the low experimental morbidity and high vaccine efficacy of DeltaipaB/inv are primarily based on high protective immune responses, which may be enhanced by the polymorphonuclear neutrophil infiltration unaccompanied by tissue injury.
|
Volume |
177(7)
|
Pages |
4709-17
|
Published |
2006-10-1
|
DOI |
10.4049/jimmunol.177.7.4709
|
PII |
177/7/4709
|
PMID |
16982910
|
MeSH |
Adhesins, Bacterial / immunology*
Animals
Antibodies, Bacterial / analysis
Dysentery, Bacillary / immunology
Dysentery, Bacillary / pathology
Dysentery, Bacillary / prevention & control*
Female
HeLa Cells
Humans
In Situ Nick-End Labeling
Inflammation / immunology
Inflammation / pathology
Lung / immunology
Lung / microbiology
Lung / pathology
Mice
Mice, Inbred BALB C
Mutation
Shigella / genetics
Shigella / immunology
Shigella Vaccines* / adverse effects
Shigella Vaccines* / immunology
Vaccines, Synthetic / immunology
|
IF |
4.886
|
Times Cited |
24
|
WOS Category
|
IMMUNOLOGY
|
Resource |
Pathogenic microorganisms |
S. flexneri ? |