| 1. |
- Ahmed, Tanvir, 1970, et al.
(författare)
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CD4+ T-cell responses to an oral inactivated cholera vaccine in young children in a cholera endemic country and the enhancing effect of zinc supplementation.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28:2, s. 422-9
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Tidskriftsartikel (refereegranskat)abstract
- Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral((R)) containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10-18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P<0.01) and IFN-gamma production (P<0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P>0.05). The IFN-gamma production was significantly higher (P<0.01) but the blast formation comparable (P>0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P<0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-gamma as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.
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| 2. |
- Ahmed, Tanvir, 1970, et al.
(författare)
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Children with the Le(a+b-) blood group have increased susceptibility to diarrhea caused by enterotoxigenic Escherichia coli expressing colonization factor I group fimbriae.
- 2009
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Ingår i: Infection and immunity. - 1098-5522. ; 77:5, s. 2059-64
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that children with blood group A have increased susceptibility to enterotoxigenic Escherichia coli (ETEC) diarrhea and that Lewis blood group "a" antigen (Le(a)) may be a candidate receptor for ETEC colonization factor (CF) antigen I (CFA/I) fimbriae. Based on these findings, we have attempted to determine if children with the Le(a+b-) phenotype may be more susceptible to diarrhea caused by ETEC, in particular ETEC expressing CFA/I and related fimbriae of the CFA/I group, than Le(a-b+) children. To test this hypothesis, we have determined the Lewis antigen expression in 179 Bangladeshi children from a prospective birth cohort study in urban Dhaka in which ETEC expressing major CFs such as CFA/I, CS3, CS5, and CS6 was the most commonly isolated diarrhea pathogen during the first 2 years of life. The Lewis blood group phenotypes were determined by a dot blot immunoassay using saliva samples and by a tube agglutination test using fresh red blood cells. The results indicate that Le(a+b-) children more often had symptomatic than asymptomatic ETEC infections (P < 0.001), whereas symptomatic and asymptomatic ETEC infections were equally frequent in Le(a-b+) children. We also show that children with the Le(a+b-) blood type had significantly higher incidences of diarrhea caused by ETEC expressing fimbriae of the CFA/I group than Le(a-b+) children (P < 0.001). In contrast, we did not find any association between the Lewis blood group phenotype and diarrhea caused by ETEC expressing CS6 or rotavirus.
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| 3. |
- Ahmed, Tanvir, 1970, et al.
(författare)
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Enhanced immunogenicity of an oral inactivated cholera vaccine in infants in Bangladesh obtained by zinc supplementation and by temporary withholding breast-feeding.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 27:9, s. 1433-9
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Tidskriftsartikel (refereegranskat)abstract
- The killed oral cholera vaccine Dukoral is recommended for adults and only children over 2 years of age, although cholera is seen frequently in younger children and there is an urgent need for a vaccine for them. Since decreased immunogenicity of oral vaccines in children in developing countries is a critical problem, we tested interventions to enhance responses to Dukoral. We evaluated the effect on the immune responses by temporarily withholding breast-feeding or by giving zinc supplementation. Two doses of Dukoral consisting of killed cholera vibrios and cholera B subunit were given to 6-18 months old Bangladeshi children (n=340) and safety and immunogenicity studied. Our results showed that two doses of the vaccine were safe and induced antibacterial (vibriocidal) antibody responses in 57% and antitoxin responses in 85% of the children. Immune responses were comparable after intake of one and two doses. Temporary withholding breast-feeding for 3 h before immunization or supplementation with 20 mg of zinc per day for 42 days resulted in increased magnitude of vibriocidal antibodies (77% and 79% responders, respectively). Administration of vaccines without buffer or in water did not result in reduction of vibriocidal responses. This study demonstrates that the vaccine is safe and immunogenic in children under 2 years of age and that simple interventions can enhance immune responses in young children.
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| 4. |
- Ahmed, Tanvir, 1970
(författare)
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Vaccination against cholera and ETEC diarrhea and interventions to improve vaccine immune responses.
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vaccination against cholera and ETEC diarrhea and interventions to improve vaccine immune responses Abstract Vibrio cholerae O1 and enterotoxigenic Escherichia coli (ETEC) together account for the majority of bacterial causes of acute dehydrating diarrhea in children in Bangladesh. Vaccines should be considered as an important public health tool for prevention of these diarrheal diseases. However, a limitation for the use of vaccines in developing countries is that the efficacy and immunogenicity of vaccines, especially oral enteric vaccines, are lower in these countries than in the industrialized world. The main objectives of the thesis were to study the safety and immunogenicity of oral cholera toxin B subunit (CTB) containing inactivated whole cell ETEC and cholera vaccines in young children in a developing country and to identify possible immune modulating factors, e.g. vaccine dose, different buffer formulations, effects of breast milk withholding and zinc supplementation. For determining optimal doses of the ETEC vaccine, we immunized 6 months to 12 year old children with full, half and quarter doses of the ETEC vaccine. Safety and immunogenicity of different vaccine doses were compared. All doses of the ETEC vaccine were found to be equally immunogenic in the older children. However, a quarter dose, although giving somewhat lower antibacterial responses than a full dose, was required for children 6-18 months to avoid reactogenicity. For determining the safety and immunogenicity of the cholera vaccine in young children and the effect of different interventions to try to enhance immune responses, children 6-18 months of age were given two doses of the vaccine according to the standard protocol or with different modifications. In addition to analyzing antibacterial and antitoxic B-cell responses, T-cell responses were determined using a new flowcytometric technique, FASCIA. The vaccine was found to be safe and to induce both antibody and Th1 type T-cell responses. Vibriocidal antibody responses were improved by temporarily withholding breast-feeding for three hours before immunization as well as by giving 20 mg of zinc from 3 weeks prior to and one week after the second dose of vaccine. Zinc supplementation also enhanced IFN-gamma responses to CTB. Further objectives of this thesis were to analyze the immune responses to one of the most prevalent ETEC colonization factors (CFs), i.e. CS6, in patients infected with CS6-positive ETEC and to evaluate if there is an association between expression of certain Lewis blood group antigens of the host and infection by ETEC expressing different CFs. Natural infection with CS6 ETEC was found to induce robust systemic and mucosal immune responses in 70-90% of adults and children with diarrhea caused by CS6 positive ETEC strains, suggesting that CS6 could be an important immunogenic component of a new ETEC vaccine. We could also show that individuals with Le (a+b-) blood group had increased susceptibility to infection with ETEC expressing CFA/I group fimbriae. The results of these studies give important background information regarding the possibility of inducing effective immune responses to oral inactivated enteric vaccines in young children in developing countries.
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| 5. |
- Shamsuzzaman, Sohel, et al.
(författare)
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Robust gut associated vaccine-specific antibody-secreting cell responses are detected at the mucosal surface of Bangladeshi subjects after immunization with an oral killed bivalent V. cholerae O1/O139 whole cell cholera vaccine: comparison with other mucosal and systemic responses.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 27:9, s. 1386-92
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of V. cholerae O139 serogroup of V. cholerae capable of causing severe dehydrating cholera has over the decade led to efforts in formulation of vaccines to protect against this pathogen. Although the prevalence of diarrhea due to V. cholerae O139 has recorded a decrease, efforts on vaccine development continues to formulate an oral vaccine capable of stimulating the gut mucosal system. We have studied the mucosal immunogenicity in Bangladeshi adults to a killed whole cell (WC) bivalent cholera vaccine composed of V. cholerae O139 as well as V. cholerae O1 strains together with the recombinant cholera toxin B subunit (CTB) (WC-O1/O139/CTB) and compared the immune responses to that obtained with the licensed monovalent cholera vaccine, Dukoral (WC-O1/CTB). Direct estimation of the WC-O1/O139/CTB vaccine-specific mucosal responses were carried out using lymphocytes isolated from duodenal biopsies, intestinal lavage fluid and feces. The vaccine induced robust antibody-secreting cell responses in the duodenum specific to CTB as well as the O1 and O139 lipopolysaccharide (LPS). Magnitude of response was higher in the gut than in the circulation in all three antibody isotypes. The CTB and LPS-specific mucosal antibody responses were also seen in intestinal lavage fluid and fecal extracts. Vibriocidal antibody responses in plasma were observed to both the V. cholerae O1 and O139 serogroups (76% and 57% response rates, respectively). Plasma IgA and IgG responses to CTB and IgA responses to both O1 and O139 LPS were elevated. The immune responses were comparable to that seen to the monovalent WC-O1/CTB recipients in all components studied. Overall, the bivalent cholera vaccine induces strong mucosal responses and the addition of the O139 component does not interfere with the responses to the licensed vaccine Dukoral. This sets the ground for testing such vaccines in large field trials in Bangladesh and also demonstrates that addition of other vibrio components to the existing cholera vaccine does not alter the responses to the O1 vaccine components.
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