| 1. |
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| 2. |
- Rattik, Sara, et al.
(författare)
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B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice
- 2018
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 111, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an important role for B cells in mucosal tolerance, in particular by induction of regulatory B (Bregs) and T cells (Tregs). In this study, we aimed to investigate if transfer of B cells pulsed with CTB-p210 can protect against atherosclerosis. Method and results: First, we studied if CTB-p210 can induce Bregs and Tregs in vitro. After pulsing B cells from Apob(tm2gy)ldlr(-/-) or Apoe(-/-) mice with CTB-p210 for 1 h and co-culturing them with naive T cells for 48 h, we observed increased expression of membrane bound TGF beta/latency-associated peptide (mTGF beta/LAP) on B cells and an increased proportion of CD25(hi)FoxP3(+) Tregs. Adoptive transfer of B cells pulsed with CTB-p210 into high-fat diet-fed Apoe(-/-) mice at 8, 10 and 12 weeks of age, reduced the plaque area in the aorta at 20 weeks of age as compared with control-treated (CTB-pOVA treated B cells or PBS) mice. Moreover, mice receiving p210-CTB treated B cells had increased levels of anti-p210 IgG antibodies. Conclusion: Our observations suggest that CTB-p210 pulsed B cells acquire a regulatory phenotype and induce Tregs in vitro. Adoptive transfer of CTB-p210, but not control-treated, B cells into Apoe(-/-) mice decreased atherosclerosis development.
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| 3. |
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| 4. |
- Yao Mattisson, Ingrid, et al.
(författare)
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Immune responses against oxidized LDL as possible targets for prevention of atherosclerosis in systemic lupus erythematosus
- 2021
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 140
-
Tidskriftsartikel (refereegranskat)abstract
- Patients suffering from systemic lupus erythematosus (SLE) are at increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. To investigate the possible role of oxidized LDL autoimmunity in the accelerated atherosclerosis associated with SLE we used a hypercholesterolemic SLE mouse model (B6.lpr.ApoE−/− mice). Promoting LDL tolerance through mucosal immunization with an apolipoprotein B-100 peptide p45 (amino acids 661–680) and cholera toxin B-subunit fusion protein increased regulatory T cells and B cells in mesenteric lymph nodes and reduced plaque development in the aorta by 33%. Treatment with the oxidized LDL-specific antibody Orticumab reduced aortic atherosclerosis by 43%, subvalvular plaque area by 50% and the macrophage content by 31%. The present study provides support for oxLDL as a possible target for prevention of cardiovascular complications in SLE. © 2021 The Author(s)
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| 5. |
- Adamsson, Jenni, 1977, et al.
(författare)
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Novel immunostimulatory agent based on CpG oligodeoxynucleotide linked to the nontoxic B subunit of cholera toxin.
- 2006
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 176:8, s. 4902-13
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we report the development of a novel, rationally designed immunostimulatory adjuvant based on chemical conjugation of CpG oligodeoxynucleotide (ODN) to the nontoxic B subunit of cholera toxin (CTB). We demonstrate that the immunostimulatory effects of CpG can be dramatically enhanced by conjugation to CTB. Thus, CpG ODN linked to CTB (CTB-CpG) was shown to be a more potent stimulator of proinflammatory cytokine and chemokine responses in murine splenocytes and human PBMCs than those of CpG ODN alone in vitro. The presence of CpG motif, but not modified phosphorothioate ODN backbone, was found to be critical for the enhanced immunostimulatory effects of CTB-CpG. Our mode-of-action studies, including studies on cells from specifically gene knockout mice suggest that similar to CpG, CTB-CpG exerts its immunostimulatory effects through a TLR9/MyD88- and NF-kappaB-dependent pathway. Surprisingly, and as opposed to CpG ODN, CTB-CpG-induced immunity was shown to be independent of endosomal acidification and resistant to inhibitory ODN. Furthermore, preincubation of CTB-CpG with GM1 ganglioside reduced the immunostimulatory effects of CTB-CpG to those of CpG ODN alone. Interestingly, conjugation of CpG ODN to CTB confers an enhanced cross-species activity to CpG ODN. Furthermore, using tetanus toxoid as a vaccine Ag for s.c. immunization, CTB-CpG markedly enhanced the Ag-specific IgG Ab response and altered the specific pattern of Ab isotypes toward a Th1 type response. To our knowledge, CTB is the first nontoxic derivative of microbial toxins discovered that when chemically linked to CpG remarkably augments the CpG-mediated immune responses.
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| 6. |
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| 7. |
- Ali, Mohammad, et al.
(författare)
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Vaccine Protection of Bangladeshi infants and young children against cholera: implications for vaccine deployment and person-to-person transmission.
- 2008
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Ingår i: The Pediatric infectious disease journal. - 0891-3668. ; 27:1, s. 33-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Killed oral cholera vaccines are internationally licensed for older children and adults, but not for infants and young children. We investigated whether mass immunization of older children and adults can confer herd protection to children too young to be vaccinated. METHODS: We analyzed the first year of surveillance of an individually randomized, placebo-controlled trial of killed oral cholera vaccines in 89,596 older Bangladeshi children and adult women. Vaccine herd protection of children less than 2 years of age, who were too young to participate in the trial, was evaluated by determining whether the incidence of cholera during the first year of follow-up of this age group was lower in residential clusters with higher levels of vaccine coverage than in clusters with lower levels of vaccine coverage. RESULTS: Vaccine coverage of the targeted population ranged from 4% to 65% in different clusters. The incidence (cases per 1000) of cholera among children less than 2 years of age ranged from 18.9 in clusters in the lowest quintile of vaccine coverage to 8.6 in clusters in the highest quintile (P = 0.004 for the inverse association between vaccine coverage and risk of cholera) Vaccine coverage of adult women (relative risk of cholera = 0.95 for each percent increase in vaccine coverage; 95% confidence interval: 0.92-0.99; P < 0.01), but not of older children, was independently associated with a lower risk of cholera in children less than 2 years of age. CONCLUSIONS: Vaccination of older age groups was associated with protection of children too young to be vaccinated. The pronounced herd protection of young children associated with vaccination of adult women suggests that adult women may play a prominent role in the transmission of cholera to young children in this setting.
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| 8. |
- 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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| 9. |
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| 10. |
- 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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| 11. |
- 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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| 12. |
- Bhattacharya, S. K., et al.
(författare)
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5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: A cluster-randomised, double-blind, placebo-controlled trial
- 2013
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Ingår i: Lancet. Infectious Diseases. - 1473-3099 .- 1474-4457. ; 13:12, s. 1050-1056
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. Methods: In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. Findings: 69 of 31932 recipients of vaccine and 219 of 34968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Interpretation: Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Funding: Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. © 2013 Elsevier Ltd.
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| 13. |
- Bhattacharya, S, et al.
(författare)
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Public health. The cholera crisis in Africa.
- 2009
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 324:5929
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Forskningsöversikt (refereegranskat)abstract
- Long-lasting cholera outbreaks in Africa suggest limitations in the current strategy of disease control.
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| 14. |
- Borde, Annika, 1979, et al.
(författare)
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Effect of protein release rates from tablet formulations on the immune response after sublingual immunization
- 2012
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 47:4, s. 695-700
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Tidskriftsartikel (refereegranskat)abstract
- Dry vaccine formulations for sublingual administration would provide great advantages for public health use, especially in developing countries, since they are easy to administer and might also have improved stability properties. This study investigates the influence of protein release rate from mucoadhesive twolayer tablets on the elicited antibody responses after sublingual immunization. Two fast release tablets, one based on a mixture of lactose and microcrystalline cellulose (MCC) and one protein coated ethylcellulose (EC) tablet, and three hydrophilic matrix tablets with extended release (ER) properties based on HPMC 90 SH 100000 or Carbopol® 974-P NF were tested. The in vitro release profiles of the model protein ovalbumin (OVA) from these tablets were characterized and correlated to the in vivo potential of the tablets to induce an immune response after sublingual immunization in BALB/c mice. It could be concluded that a tablet with fast protein release elicits antibody titres not significantly different from titres obtained with OVA in solution, whereas low immune responses were observed with a slow release of OVA from the ER formulations. Thus, an ER tablet seems not favorable for vaccine delivery to the sublingual mucosa. Thus, we can present a fast releasing tablet formulation with attractive features for sublingual immunization, whereas the use of ER formulations for sublingual vaccination has to be investigated more in detail.
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| 15. |
- Borde, Annika, 1979, et al.
(författare)
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Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation
- 2011
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 79:3, s. 508-518
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Tidskriftsartikel (refereegranskat)abstract
- Different oral liquid cholera vaccines have proved to be safe and effective, but their formulations present problems for use in low-income countries, since large package volumes have to be transported and cold chain maintenance is required. A solid state formulation would here be more advantageous, and consequently, the possibility to develop a dry cholera vaccine formulation by freeze-drying was investigated. The ability of sucrose, trehalose and mannitol to provide process stabilization during freeze-drying was tested on a formalin-killed whole-cell Vibrio cholerae model vaccine. A matrix of sucrose or trehalose prevented bacterial aggregation, preserved cell morphology and maintained practically completely the protective lipopolysaccharide (LPS) antigen on the cell surface and its reactivity with specific antibody in vitro. After reconstitution, this formulation also retained the capacity to elicit a strong serum and gut mucosal anti-LPS antibody response in orally immunized mice, as compared to the corresponding liquid vaccine formulation. The full preservation of the in vivo immunogenicity was also maintained when the internationally widely licensed oral cholera vaccine Dukoral (TM), which comprises a cocktail of inactivated V. cholerae together with cholera toxin B-subunit (CTB), was freeze-dried using sucrose for stabilization. Thus, we present a process generating a dry oral inactivated whole-cell cholera vaccine formulation with attractive features for public health use in cholera-afflicted settings.
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| 16. |
- Borde, Annika, 1979, et al.
(författare)
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Preparation and preclinical evaluation of a freeze-dried formulation of a novel combined multivalent whole-cell/B-subunit oral vaccine against enterotoxigenic Escherichia coli diarrhea
- 2016
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Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 108, s. 18-24
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Tidskriftsartikel (refereegranskat)abstract
- A promising liquid killed multivalent whole-cell plus enterotoxin B-subunit oral vaccine against enterotoxigenic Escherichia coli (ETEC), the primary cause of diarrhea among children in low-income countries and travelers to these areas, has recently been developed and tested in preclinical and phase-I and phase-II clinical studies. The vaccine contains killed E. coli bacteria over-expressing the main ETEC colonization factors (CFs) CFA/I, CS3, C5 and C6, and a recombinant enterotoxin B subunit protein (LCTBA) given together with a recently developed enterotoxin-derived adjuvant, dmLT. A dry-powder vaccine formulation should be advantageous especially for use in low-income countries. Here we describe a method to produce a dry-powder formulation by freeze-drying of the vaccine using inulin as stabilizer. Although not completely preventing aggregation of bacteria during freeze-drying, the stabilizer provided both improved overall bacterial morphology and almost complete recovery of the CF and B subunit antigens. Most importantly, oral-intragastric immunization of mice with the freeze-dried vaccine together with dmLT adjuvant elicited strong intestinal mucosal and serum antibody responses against all vaccine antigens, which were comparable to those achieved with the liquid vaccine. Our results indicate the feasibility to use freeze-drying with inulin as stabilizer for preparing a dry-powder formulation of the novel ETEC vaccine with retained oral-mucosal immunogenicity compared to the liquid formulation. © 2016 Elsevier B.V.
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| 17. |
- Bromander, A K, et al.
(författare)
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Cholera toxin enhances alloantigen presentation by cultured intestinal epithelial cells.
- 1993
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Ingår i: Scandinavian journal of immunology. - 0300-9475. ; 37:4, s. 452-8
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we show that cholera toxin (CT) strongly potentiates antigen presentation by intestinal epithelial cells, probably by enhancing co-stimulation. This was demonstrated in an allogeneic system using cells from the IEC-17 rat epithelial cell line as antigen presenting cells (APC). These cells were induced by optimal concentrations of IFN-gamma to express good amounts of Ia antigen and cultured for 24-48 h in the presence or absence of CT. Thereafter the cells were thoroughly washed and added to cultures containing MHC-incompatible spleen cells as responder cells. Epithelial cells exposed to CT demonstrated greatly enhanced ability to trigger allogen-specific T-cell proliferation as compared with IEC-17 cells treated with IFN-gamma alone. The mechanism for the enhanced APC function was investigated by analysing CT-treated IEC-17 cells for increased class II MHC antigen expression or enhanced production of cytokines with known co-stimulatory function. We found no significant increase in class II MHC antigen expression. By contrast, CT strongly promoted, in a dose-dependent fashion, the production of both IL-1 and IL-6 cytokines by IEC-17 cells as compared with untreated epithelial cells. This effect of CT was specific and not due to contaminating endotoxin because excess amounts of soluble toxin receptor, ganglioside GM1, added to the IEC-17 cultures completely abrogated the cytokine response to CT. These results together with our previous findings of enhanced antigen presentation by macrophages stimulated by CT suggest that the potent adjuvant function of CT for induction of mucosal immune responses might be attributed to an enhanced co-stimulating ability of several putative APC in the mucosal immune system: macrophages, B cells and epithelial cells.
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| 18. |
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| 19. |
- Cheng, Chunmei, et al.
(författare)
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Induction of protective immunity by vaccination against Chlamydia trachomatis using the major outer membrane protein adjuvanted with CpG oligodeoxynucleotide coupled to the nontoxic B subunit of cholera toxin.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 27:44, s. 6239-46
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Tidskriftsartikel (refereegranskat)abstract
- The present study was undertaken to test the efficacy of immunization with the native major outer membrane protein (nMOMP) of Chlamydia trachomatis mouse pneumonitis (MoPn) serovar in combination with a novel immunostimulatory adjuvant consisting of CpG oligodeoxynucleotide (ODN) linked to the nontoxic B subunit of cholera toxin (CTB-CpG) to elicit a protective immune response to C. trachomatis. High levels of Chlamydia-specific IgG antibodies were detected in the sera from BALB/c mice immunized intramuscularly and subcutaneously (i.m.+s.c.) with the nMOMP/CTB-CpG vaccine or with nMOMP adjuvanted with a mixture of CT and CpG ODN (CT+CpG). Further, these immunization schemes gave rise to significant T-cell-mediated Chlamydia-specific immune responses. No Chlamydia-specific humoral or cell-mediated immune responses were detected in the control mice vaccinated with ovalbumin together with either CTB-CpG or CT+CpG. Following an intranasal challenge with C. trachomatis the groups of mice immunized with nMOMP plus CTB-CpG, CT+CpG or live C. trachomatis were found to be protected based on their change in body weight and lung weight as well as number of inclusion forming unit recovered from the lungs, as compared with control groups immunized with ovalbumin plus either adjuvants. Interestingly, IFN-gamma-producing CD4(+), but not CD8(+), T-cells showed a significant correlation with the outcomes of the challenge. In conclusion, nMOMP in combination with the novel adjuvant CTB-CpG elicited a significant antigen-specific antibody and cell-mediated immune responses as well as protection against a pulmonary challenge with C. trachomatis.
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| 20. |
- Chowdhury, F., et al.
(författare)
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A phase I/II study to evaluate safety, tolerability and immunogenicity of Hillchol®, an inactivated single Hikojima strain based oral cholera vaccine, in a sequentially age descending population in Bangladesh
- 2021
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 39:32, s. 4450-4457
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization (WHO) recommends the use of oral cholera vaccines (OCVs) as part of an integrated control program, both in highly endemic settings and during cholera epidemics. The available and internationally recommended WHO-prequalified OCVs (Dukoral, Shanchol, Euvichol) contain multiple heat and formalin-killed V. cholerae strains of Inaba and Ogawa serotypes. MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd. in technical collaboration with University of Gothenburg, Sweden has developed a new single strain OCV, Hillchol. This vaccine consists of formaldehyde-inactivated whole cell El Tor V. cholerae O1 bacteria engineered into the Hikojima serotype for stable expression of both the Ogawa (AB) and Inaba (AC) LPS antigens on the bacterial surface. We evaluated the safety and immunogenicity of this novel and potentially much less expensive OCV in comparison with Shanchol. Methods: We conducted a randomized, non-inferiority, age-descending clinical trial of OCV (Hillchol vs. Shanchol) in the Mirpur area of Dhaka city from July 2016 to May 2017. This study was carried out in three different age cohorts (1–<5, 5–17 and ≥18 years old). Two doses of vaccine were given at 14 days intervals to 560 healthy participants. Findings: No serious adverse events were reported. There were no significant differences in the rates of adverse events between the test vaccine (Hillchol) and the comparator (Shanchol) group. Serum vibriocidal antibody responses in all age groups combined were comparable for all the O1 Ogawa (59% vs. 67%; 90% CI of difference: −14.55, −0.84) and Inaba (70% vs. 71%; 90% CI of difference: −7.24, 5.77) serotypes, showing that the Hillchol vaccine was non-inferior to Shanchol. This new vaccine was also non-inferior to Shanchol in the different age strata. Conclusion: The safety and immunogenicity profile of the new OCV Hillchol is comparable to Shanchol in persons residing in a cholera-endemic setting. ClinicalTrials.gov number: NCT02823899. © 2021
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| 21. |
- Clemens, John D., et al.
(författare)
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Cholera
- 2017
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 390, s. 1539-1549
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Forskningsöversikt (refereegranskat)abstract
- © 2017 Elsevier Ltd Cholera is an acute, watery diarrhoeal disease caused by Vibrio cholerae of the O1 or O139 serogroups. In the past two centuries, cholera has emerged and spread from the Ganges Delta six times and from Indonesia once to cause global pandemics. Rational approaches to the case management of cholera with oral and intravenous rehydration therapy have reduced the case fatality of cholera from more than 50% to much less than 1%. Despite improvements in water quality, sanitation, and hygiene, as well as in the clinical treatment of cholera, the disease is still estimated to cause about 100 000 deaths every year. Most deaths occur in cholera-endemic settings, and virtually all deaths occur in developing countries. Contemporary understanding of immune protection against cholera, which results from local intestinal immunity, has yielded safe and protective orally administered cholera vaccines that are now globally stockpiled for use in the control of both epidemic and endemic cholera.
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| 22. |
- Clemens, John, et al.
(författare)
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Development of pathogenicity-driven definitions of outcomes for a field trial of a killed oral vaccine against enterotoxigenic Escherichia coli in Egypt: application of an evidence-based method
- 2004
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Ingår i: J Infect Dis. ; 189:12, s. 2299-307
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To design an efficacy trial of a killed oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea in Egyptian children, we derived for ETEC diarrhea an empirical definition that increased the probability that diarrhea associated with excretion of ETEC was caused by the detected ETEC. METHODS: We conducted a cohort study of 397 Egyptian children <24 months old and monitored them until they were 3 years old. Vaccine-preventable (VP) ETEC was defined as ETEC expressing >/=1 of the toxin- (heat-labile [LT] toxin) and colonization-factor antigens (CFA I, II, and IV) in the vaccine. RESULTS: Although fecal excretion of VP-ETEC was highly associated with diarrhea, excretion of LT-ETEC per se was not related to diarrhea (adjusted odds ratio [OR(A)], 1.16 [95% confidence interval [CI], 0.90-1.49]). The fecal excretion of antigenic types of VP-ETEC other than LT-ETEC (non-LT VP-ETEC) was highly associated with diarrheal symptoms (OR(A), 3.91 [95% CI, 2.78-5.49]; P<.001), and this association was greater for nonbloody than for bloody diarrhea. CONCLUSIONS: Because the vaccine had been anticipated to protect primarily against symptomatic ETEC diarrhea, these results indicate that the primary-outcome definition of ETEC diarrhea for the trial should be restricted to nonbloody diarrheal episodes associated with fecal excretion of non-LT VP-ETEC.
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| 23. |
- Clemens, John, et al.
(författare)
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New-generation vaccines against cholera
- 2011
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Ingår i: NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY. - 1759-5045. ; 8:12, s. 701-710
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Forskningsöversikt (refereegranskat)abstract
- Cholera is a major global health problem, causing approximately 100,000 deaths annually, about half of which occur in sub-Saharan Africa. Although early-generation parenteral cholera vaccines were abandoned as public health tools owing to their limited efficacy, newer-generation oral cholera vaccines have attractive safety and protection profiles. Both killed and live oral vaccines have been licensed, although only killed oral vaccines are currently manufactured and available. These killed oral vaccines not only provide direct protection to vaccinated individuals, but also confer herd immunity. The combination of direct vaccine protection and vaccine herd immunity effects makes these vaccines highly cost-effective and, therefore, attractive for use in developing countries. Administration of these oral vaccines does not require qualified medical personnel, which makes their use practical--even in developing countries. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches, especially improved water quality and sanitation, they represent important tools in the public health armamentarium to control both endemic and epidemic cholera.
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| 24. |
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| 25. |
- Clemens, John, et al.
(författare)
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When, How, and Where can Oral Cholera Vaccines be Used to Interrupt Cholera Outbreaks?
- 2014
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Ingår i: Cholera Outbreaks. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0070-217X. ; 379, s. 231-258
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Tidskriftsartikel (refereegranskat)abstract
- Cholera continues to be a major global health problem, at times causing major and prolonged outbreaks in both endemic and nonendemic settings in developing countries. While improved water quality, sanitation, and hygiene (WASH) will provide the ultimate solution to prevention of this disease burden, this is a far-off goal for most developing countries. Oral cholera vaccines (OCVs) have been demonstrated to be effective in the control of cholera outbreaks, and constitute useful tools to be used in conjunction with efforts to improve WASH. Two killed OCVs are prequalified by WHO for purchase by UN agencies for international use. Recently, WHO has launched a global stockpile of killed OCVs for use to control outbreaks. Rational deployment of OCV from this stockpile will require consideration of costs, feasibility, disease epidemiology, and the protective characteristics of the vaccine deployed, as well as effective and rapid coordination of processes and logistics used to make decisions on deployment and delivery of the vaccine to the population in need. Despite not having data on all the questions of relevance as to how to use OCVs to control cholera outbreaks in different settings, there is clearly more than enough evidence to initiate their use, as answers to remaining questions and refinement of policies will mainly come with experience.
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