Live, orally administered, attenuated vaccine strains of Vibrio cholerae have many theoretical advantages over killed vaccines. A single oral inoculation could result in intestinal colonization and rapid immune responses, obviating the need for repetitive dosing. Live V. cholerae organisms can also respond to the intestinal environment and immunological exposure to in vivo expressed bacterial products, which could result in improved immunological protection against wild-type V. cholerae infection. The concern remains that live oral cholera vaccines may be less effective among partially immune individuals in cholera endemic areas as pre-existing antibodies can inhibit live organisms and decrease colonization of the gut. A number of live oral cholera vaccines have been developed to protect against cholera caused by the classical and El Tor serotypes of V. cholerae O1, including CVD 103-HgR, Peru-15 and V. cholerae 638. A number of live oral cholera vaccines have also been similarly developed to protect against cholera caused by V. cholerae O139, including CVD 112 and Bengal-15. Live, orally administered, attenuated cholera vaccines are in various stages of development and evaluation.

1998-02-01·Infection and Immunity2区 · 医学

Investigation of the Roles of Toxin-Coregulated Pili and Mannose-Sensitive Hemagglutinin Pili in the Pathogenesis of Vibrio cholerae O139 Infection

2区 · 医学

Article

作者: Losonsky, Genevieve ; Taylor, Ronald K. ; Kaper, James B. ; Levine, Myron M. ; Lim, Yu ; Nataro, James P. ; Tacket, Carol O.

ABSTRACT In this study, adult volunteers were fed tcpA and mshA deletion mutants of V. cholerae O139 strain CVD 112 to determine the role of toxin-coregulated pili (TCP) and mannose-sensitive hemagglutinin (MSHA) in intestinal colonization. Eight of 10 volunteers who received CVD 112 or CVD 112 Δ mshA shed the vaccine strains in their stools; the geometric mean peak excretion for both groups was 1.4 × 10 5 CFU/g of stool. In contrast, only one of nine recipients of CVD 112 Δ tcpA shed vibrios in his stool ( P < 0.01); during the first 24 h after inoculation, 3 × 10 2 CFU/g was recovered from this volunteer. All recipients of CVD 112 and 8 (80%) of the recipients of CVD 112 Δ mshA developed at least a fourfold rise in vibriocidal titer after immunization. In contrast, only one (11%) of the nine recipients of CVD 112 Δ tcpA developed a fourfold rise in vibriocidal titer ( P < 0.01). We conclude that TCP are an important colonization factor of V. cholerae O139 and probably of El Tor V. cholerae O1. In contrast, MSHA does not appear to promote intestinal colonization in humans.

1997-05-01·Clinical Diagnostic Laboratory Immunology

Vibriocidal antibody responses in North American volunteers exposed to wild-type or vaccine Vibrio cholerae O139: specificity and relevance to immunity

Article

作者: Tacket, C O ; Comstock, L E ; Lim, Y ; Levine, M M ; Johnson, J A ; Morris, J G ; Kaper, J B ; Motamedi, P ; Losonsky, G A

The emergence of a new agent of cholera, Vibrio cholerae O139, has prompted a reevaluation of the vibriocidal antibody assay. This assay, primarily directed to lipopolysaccharide, is an important correlate of O1 immunity. V. cholerae O139 strains are encapsulated, rendering them relatively resistant to killing by serum. Recent reports suggest that there is strain-to-strain variability in the sensitivity of the vibriocidal assay to fully encapsulated O139 strains. We have assessed a modified vibriocidal assay for fully encapsulated O139 strain AI-1837 and its unencapsulated mutant 2L in sera from 53 volunteers given wild-type AI-1837 or its attenuated derivative CVD 112 and from 48 controls challenged with V. cholerae O1 or strains of the family Enterobacteriaceae. Vibriocidal responses to the AI-1837 and 2L strains were seen in 67 and 89% of volunteers, respectively, following a single exposure to the wild-type strain. However, >50% of all controls had low-level vibriocidal responses to both strains. These nonspecific responses were transient and of the immunoglobulin G isotype. No binding activity against purified O139 lipopolysaccharide (LPS) by immunoblotting was seen in control sera. In contrast, vibriocidal assay and strain 2L LPS responses by immunoblotting were detectable in 91% of tested volunteers following a single exposure to O139. The presence of vibriocidal antibody to AI-1837 or 2L was not associated with protection in rechallenge studies with O139 strain AI-1837. The vibriocidal assay with unencapsulated strain 2L may be used to detect exposure to O139 strain AI-1837 in controlled research trials. However, its lack of specificity does not make it useful for determining exposure to V. cholerae O139 in the field.

100 项与 Cholera vaccine CVD 112(Crucell) 相关的药物交易

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