Affiliation:
1. Center for Vaccine Development and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201
2. Department of Microbiology, Immunology and Biochemistry, Morehouse School of Medicine, Atlanta, Georgia 30310
Abstract
ABSTRACT
The induction of interleukin-8 (IL-8) in vitro has been suggested to correlate with the reactogenicity of
Vibrio cholerae
vaccine candidates.
V. cholerae
vaccine candidate 638, a hemagglutinin protease/
hap-
defective strain, was recently reported to be well tolerated in human volunteers, suggesting a role for Hap in reactogenicity. We examined the role of
hap
in the induction of IL-8 in intestinal epithelial T84 cells. Wild-type
V. cholerae
strains 3038 and C7258 and a vaccine candidate strain, JBK70, induced levels of IL-8 similar to those of their isogenic
hap
mutants. Supernatant containing Hap did not stimulate IL-8 production at a variety of concentrations tested, suggesting that Hap itself does not induce IL-8 production. Furthermore, supernatant from CVD115, which had deletions of
hap
and
rtxA
(encoding repeats in toxin) and was derived from a reactogenic strain, CVD110, induced IL-8 production in T84 cells in a dose-dependent manner. The IL-8-stimulating activity of CVD115 culture supernatants was growth phase dependent and was strongest in stationary phase cultures. This IL-8 stimulator(s) was resistant to heat treatment but sensitive to proteinase. Protease activity in vitro did not correlate with the reactogenicity of
V. cholerae
vaccine candidates. Our data suggest that Hap is not an IL-8 inducer in T84 cells and that the IL-8 stimulator in the supernatant of
V. cholerae
culture may play a role in reactogenicity.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
26 articles.
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