| 1. |
- Anh, Dang Duc, et al.
(författare)
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Safety and immunogenicity of a reformulated Vietnamese bivalent killed, whole-cell, oral cholera vaccine in adults.
- 2007
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 25:6, s. 1149-55
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Tidskriftsartikel (refereegranskat)abstract
- Vietnam currently produces an orally administered, bivalent (O1 and O139) killed whole-cell vaccine and is the only country in the world with endemic cholera to use an oral cholera vaccine in public health practice. In order to allow international use, the vaccine had to be reformulated to meet World Health Organization (WHO) requirements. We performed a randomized, placebo controlled, safety and immunogenicity studies of this reformulated vaccine among Vietnamese adults. One hundred and forty-four subjects received the two-dose regimen and 143 had two blood samples obtained for analysis. We found that this reformulated oral killed whole-cell cholera vaccine was safe, well tolerated and highly immunogenic.
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| 2. |
- Attridge, Stephen, 1951, et al.
(författare)
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Detection of antibodies to toxin-coregulated pili in sera from cholera patients
- 2004
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Ingår i: Infect Immun. ; 72:3, s. 1824-7
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies (MAbs) were prepared against toxin-coregulated pili (TCP) isolated from Vibrio cholerae O1 El Tor. Despite their limited bactericidal potential, two MAbs were able to mediate biotype-specific protection against experimental cholera in infant mice. These MAbs were used in immunoblotting studies to assess seroconversion to El Tor TCP following cholera. Clear anti-pilus responses were observed in five of nine patients.
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| 3. |
- Attridge, Stephen, 1951, et al.
(författare)
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Differential immunogenicity of Vibrio cholerae O139 variants expressing different combinations of naturally occurring and atypical forms of the serogroup polysaccharide.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 27:7, s. 1055-61
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Tidskriftsartikel (refereegranskat)abstract
- Field testing of an inactivated bivalent O1/O139 cholera vaccine suggests that Vibrio cholerae O1 is more immunogenic than V. cholerae O139. To investigate whether this might be partly attributable to the production of capsular polysaccharide (CPS) by O139 isolates, we have compared the immunogenicity of variant strains expressing different combinations of lipopolysaccharide (LPS) and CPS. These studies indicate that the core-linked LPS structure is of paramount importance for induction of antibodies to the serogroup antigen. By contrast CPS was minimally immunogenic. Significantly the presence of CPS did not modulate the immunogenicity of the underlying LPS. To examine whether differences in LPS structure might contribute to the differing immunogenicities of the O1 and O139 serogroups, an attempt was made to modify the normal O139 LPS structure by provision of one of several heterologous wzz genes. The resulting variants displayed additional, atypical surface polysaccharide, whose modal length was characteristic for the particular wzz gene. By immunoblotting this novel material showed a ladder-like banding pattern typical of LPS, but its failure to be stained by silver indicated that it was not core-associated and was therefore more like truncated CPS. Consistent with our earlier findings, studies using systemic or mucosal routes of immunization failed to demonstrate any consistent enhancement of antibody responses associated with production of these aberrant polysaccharide polymers.
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| 4. |
- Attridge, Stephen, 1951, et al.
(författare)
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Vibrio cholerae O139 capsular polysaccharide confers complement resistance in the absence or presence of antibody yet presents a productive target for cell lysis: implications for detection of bactericidal antibodies.
- 2009
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Ingår i: Microbial pathogenesis. - : Elsevier BV. - 1096-1208 .- 0882-4010. ; 47:6, s. 314-20
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Tidskriftsartikel (refereegranskat)abstract
- Vibrio cholerae O139 variants with different surface phenotypes have been compared for their resistance to complement and also for their susceptibility to antibody-dependent, complement-mediated bacteriolysis (ACB). While both capsular polysaccharide (CPS) and lipopolysaccharide (LPS) contribute to complement resistance in the absence of antibody, the relative survival of variants expressing only one of these surface polysaccharides reveals CPS to be of much greater significance in this respect. Variants with LPS+/CPS- or LPS-/CPS+ surface phenotypes were both susceptible to ACB, showing that antibody binding to either of the O139 polysaccharides can initiate ACB. Demonstration of the lytic potential of antibodies bound to the capsule is novel and necessitates a revision of the suggested mechanism by which CPS confers partial protection of wild-type V. cholerae O139 against ACB. This finding also raised the possibility that there may be CPS-restricted epitopes which can function as substrates for ACB, which would invalidate the common practice of using unencapsulated O139 variants for estimating bactericidal responses. Since our data did not support this scenario, we evaluated several unencapsulated strains - including variants producing normal or elongated polysaccharide chains, and a hybrid O1/O139 strain - for their utility as indicators of bactericidal antibodies to V. cholerae O139. Our findings support the use of the recently-isolated CIRS134, which ensures reproducible titrations and allows assignment of high lytic titres in assays requiring only 2% complement. However low-level, cross-serogroup lytic activity was detected when CIRS134 was used to assay responses of mice injected with O1 serogroup V. cholerae, suggesting that this indicator should be used with caution when evaluating the immunogenicity of bivalent O1/O139 vaccines.
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| 5. |
- Murray, Gerald L, et al.
(författare)
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Altering the length of the lipopolysaccharide O antigen has an impact on the interaction of Salmonella enterica serovar Typhimurium with macrophages and complement.
- 2006
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Ingår i: Journal of bacteriology. - 0021-9193. ; 188:7, s. 2735-9
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Forskningsöversikt (refereegranskat)abstract
- A panel of isogenic Salmonella enterica serovar Typhimurium strains that vary only in the length of the O antigen was constructed through complementation of a wzz double mutant (displaying unregulated O-antigen length) with one of two homologous (wzzST and wzzfepE) or three heterologous (wzzO139 of Vibrio cholerae and wzzSF and wzzpHS-2Departamento de Química, Bioquímica y Biología Molecular, Universidad Cardenal Herrera-CEU, 46113 Moncada, Valencia) of Shigella flexneri) wzz genes. Each gene was functional in the S. enterica serovar Typhimurium host and specified production of O-antigen polymers with lengths typical of those synthesized by the donor bacteria (ranging from 2 to >100 O-antigen repeat units). By use of this panel of strains, it was found that O-antigen length influences invasion/uptake by macrophage cells; this is the first time this has been shown with Salmonella. O-antigen length was confirmed to be related to complement resistance, with a minimum protective length of >4 and <15 repeat units. O antigen of 16 to 35 repeat units was found to activate complement more efficiently than other lengths, but this was unrelated to complement resistance. No evidence was found to suggest that modifying the length of the O-antigen polymer affected expression of the O1, O4, or O5 antigenic factors.
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| 6. |
- Murray, Gerald L, et al.
(författare)
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Inducible serum resistance in Salmonella typhimurium is dependent on wzz(fepE)-regulated very long O antigen chains.
- 2005
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 7:13, s. 1296-304
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella typhimurium possesses two wzz genes conferring long (wzz(ST)) and very long (wzz(fepE)) lipopolysaccharide O antigen modal chain lengths. While the long O antigen modal length was essential for complement resistance, the very long modal length was found to have a minor role. However, when grown in the presence of serum, S. typhimurium demonstrated a wzz(fepE)-dependent increase in the density of very long O antigen chains, resulting in a significant increase in serum resistance. Similar phenotypic changes were observed after growth under iron-limiting conditions, though iron limitation is unlikely to be the sole signalling mechanism behind the changes induced in serum. A wzz(fepE)::lacZ promoter fusion was used to determine that regulation of wzz(fepE) transcription is unlikely to be the mechanism behind the variation in O antigen length. Since systemic infection occurs in a small but significant percentage of human non-typhoid salmonellosis, the phenomenon identified in this study may be significant during the bacteraemic phase of infection.
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| 7. |
- Nygren, Erik, et al.
(författare)
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Establishment of an adult mouse model for direct evaluation of the efficacy of vaccines against Vibrio cholerae
- 2009
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 77:8, s. 3475-3484
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Tidskriftsartikel (refereegranskat)abstract
- We describe here a new animal model that offers the prospect of using conventional adult mice for direct evaluation of the protective potential of new cholera vaccines. Pretreatment of adult mice with oral streptomycin allowed intestinal colonization by streptomycin-resistant Vibrio cholerae strains of either the O1 or the O139 serogroup. Bacteria were recovered in greatest numbers from the cecum and large intestine, but recoveries from all regions of the gut correlated significantly with bacterial excretion in fresh fecal pellets, which thus provides a convenient indicator of the extent and duration of gut colonization. Mice immunized mucosally or systemically with viable or inactivated V. cholerae were shown to be comparatively refractory to colonization after challenge with the immunizing strain. Several variables were examined to optimize the model, the most significant being the size of the challenge inoculum; surprisingly, a smaller challenge dose resulted in more consistent and sustained colonization. Studies with mutant strains unable to produce cholera toxin or toxin-coregulated pili revealed that neither factor contributed significantly to colonization potential. Protection against V. cholerae challenge was shown to be serogroup restricted, and significant inverse correlations were detected between serum and intestinal anti-lipopolysaccharide antibody responses and the levels of excretion of challenge organisms.
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| 8. |
- Nygren, Erik, 1976, et al.
(författare)
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Murine antibody responses following systemic or mucosal immunization with viable or inactivated Vibrio cholerae.
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:52, s. 6784-90
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Tidskriftsartikel (refereegranskat)abstract
- Protocols are described for the induction of strong, consistent serum and mucosal antibody responses to Vibrio cholerae O1 or O139 lipopolysaccharide (LPS) following intranasal or oral immunization of adult mice with viable or formalin-killed bacteria. A simplified two-dose schedule for intranasal immunization has been identified, whereby viable bacteria elicit strong serum responses and, most importantly, also induce significant, sustained intestinal IgA responses. Using higher doses of bacteria it was also possible to generate consistently high intestinal and serum anti-LPS responses by the oral route. The efficacy of these immunization schedules was not dependent on co-administration of adjuvant. Gut responses were estimated using two sampling techniques involving the collection of fresh faecal pellets or the preparation of intestinal tissue extracts. The significant correlation between these estimates validates the more convenient approach of measuring intestinal responses using faecal pellet extracts, which allows repeated sampling from the same animals. V. cholerae O1 and O139 were similarly immunogenic by either mucosal route. More intensive immunization schedules for administration of formalin-killed bacteria have also been defined. Using these regimes it was possible to generate serum and gut antibody responses comparable to those elicited by viable V. cholerae. The established immunization protocols will allow evaluation of the systemic and mucosal immunogenicity of new vaccine formulations.
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