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Mitchell B Cohen - One of the best experts on this subject based on the ideXlab platform.
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the live attenuated Cholera Vaccine cvd 103 hgr primes responses to the toxin coregulated pilus antigen tcpa in subjects challenged with wild type vibrio Cholerae
Clinical and Vaccine Immunology, 2017Co-Authors: Leslie M Mayosmith, Stephen B. Calderwood, Wilbur H Chen, Mitchell B Cohen, Beth D Kirkpatrick, Michael Lock, Douglas Haney, Jakub K Simon, Caroline E LyonAbstract:One potential advantage of live attenuated bacterial Vaccines is the ability to stimulate responses to antigens which are only expressed during the course of infection. To determine whether the live attenuated Cholera Vaccine CVD 103-HgR (Vaxchora) results in antibody responses to the in vivo-induced toxin-coregulated pilus antigen TcpA, we measured IgA and IgG responses to Vibrio Cholerae O1 El Tor TcpA in a subset of participants in a recently reported experimental challenge study. Participants were challenged with V. Cholerae O1 El Tor Inaba N16961 either 10 days or 90 days after receiving the Vaccine or a placebo. Neither vaccination nor experimental infection with V. Cholerae alone resulted in a robust TcpA IgG or IgA response, but each did elicit a strong response to Cholera toxin. However, compared to placebo recipients, Vaccinees had a marked increase in IgG TcpA antibodies following the 90-day challenge, suggesting that vaccination with CVD 103-HgR resulted in priming for a subsequent response to TcpA. No such difference between Vaccine and placebo recipients was observed for volunteers challenged 10 days after vaccination, indicating that this was insufficient time for Vaccine-induced priming of the TcpA response. The priming of the response to TcpA and potentially other antigens expressed in vivo by attenuated V. Cholerae may have relevance to the maintenance of immunity in areas where Cholera is endemic.
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single dose live oral Cholera Vaccine cvd 103 hgr protects against human experimental infection with vibrio Cholerae o1 el tor
Clinical Infectious Diseases, 2016Co-Authors: Wilbur H Chen, Mitchell B Cohen, Beth D Kirkpatrick, Rebecca C Brady, David Galloway, Marc Gurwith, R H Hall, Robert Kessler, Michael Lock, Douglas HaneyAbstract:BACKGROUND No licensed Cholera Vaccine is presently available in the United States. Cholera Vaccines available in other countries require 2 spaced doses. A single-dose Cholera Vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio Cholerae O1 classical Inaba Vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this Vaccine in a human Cholera challenge model. METHODS Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of Vaccine (approximately 5 × 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 10(5) CFU of wild-type V. Cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. RESULTS The Vaccine was well tolerated, with no difference in adverse event frequency among 95 Vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) Vaccinees at 10 days (Vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) Vaccinees at 3 months (Vaccine efficacy, 79.5%; P < .0001). CONCLUSIONS The significant Vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose Cholera Vaccine. CLINICAL TRIALS REGISTRATION NCT01895855.
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single dose live oral Cholera Vaccine cvd 103 hgr protects against human experimental infection with vibrio Cholerae o1 el tor
Clinical Infectious Diseases, 2016Co-Authors: Wilbur H Chen, Mitchell B Cohen, Beth D Kirkpatrick, Rebecca C Brady, David Galloway, Marc Gurwith, R H Hall, Robert Kessler, Michael Lock, Douglas HaneyAbstract:Background. No licensed Cholera Vaccine is presently available in the United States. Cholera Vaccines available in other countries require 2 spaced doses. A single-dose Cholera Vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance. PXVX0200, based on live attenuated Vibrio Cholerae O1 classical Inaba Vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this Vaccine in a human Cholera challenge model. Methods. Consenting healthy adult volunteers, 18–45 years old, were randomly allocated 1:1 to receive 1 oral dose of Vaccine (approximately 5 × 108 colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 105 CFU of wild-type V. Cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. Results. The Vaccine was well tolerated, with no difference in adverse event frequency among 95 Vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) Vaccinees at 10 days (Vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) Vaccinees at 3 months (Vaccine efficacy, 79.5%; P < .0001). Conclusions. The significant Vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose Cholera Vaccine. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT01895855","term_id":"NCT01895855"}}NCT01895855
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randomized double blind placebo controlled multicentered trial of the efficacy of a single dose of live oral Cholera Vaccine cvd 103 hgr in preventing Cholera following challenge with vibrio Cholerae o1 el tor inaba three months after vaccination
Infection and Immunity, 1999Co-Authors: Carol O Tacket, Steven S Wasserman, Genevieve Losonsky, S J Cryz, J B Kaper, Mitchell B Cohen, Karen L Kotloff, Sofie Livio, Robert R Edelman, Ralph A GiannellaAbstract:CVD 103-HgR is a live oral Cholera Vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of Cholera toxin from classical Inaba Vibrio Cholerae O1 569B; the strain also contains a mercury resistance gene as an identifying marker. This Vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. Cholerae O1. A randomized, double-blind, placebo-controlled, multicenter study of Vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderate and severe El Tor Cholera in U.S. volunteers. A total of 85 volunteers (50 at the University of Maryland and 35 at Children's Hospital Medical Center/University of Cincinnati) were recruited for vaccination and challenge with wild-type V. Cholerae El Tor Inaba. Volunteers were randomized in a double-blind manner to receive, with buffer, a single oral dose of either CVD 103-HgR (2 x 10(8) to 8 x 10(8) CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers were orally challenged with 10(5) CFU of virulent V. Cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Ninety-one percent of the Vaccinees had a >/=4-fold rise in serum vibriocidal antibodies after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 Vaccinees had moderate or severe diarrhea (>/=3-liter diarrheal stool) (P < 0.01; protective efficacy, 91%). A total of 21 (91%) of 23 placebo recipients and 5 (18%) of 28 Vaccinees had any diarrhea (P < 0.001; protective efficacy, 80%). Peak stool V. Cholerae excretion among placebo recipients was 1.1 x 10(7) CFU/g and among Vaccinees was 4.9 x 10(2) CFU/g (P < 0.001). This Vaccine could therefore be a safe and effective tool to prevent Cholera in travelers.
Regina C Larocque - One of the best experts on this subject based on the ideXlab platform.
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gut microbiota and development of vibrio Cholerae specific long term memory b cells in adults after whole cell killed oral Cholera Vaccine
Infection and Immunity, 2021Co-Authors: Denise Chac, Mohammad Murshid Alam, Amit Saha, Taufiqur Rahman Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Umme Salma, Nusrat Jahan, Edward T Ryan, Regina C LarocqueAbstract:Cholera is a diarrheal disease caused by Vibrio Cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. Cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. Cholerae and may be a major determinant of long-term protection against Cholera. Shanchol, a widely used oral Cholera Vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype or OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower abundance of Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to Vaccine antigens. Our results suggest the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential Vaccine adjuvants is warranted.
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the gut microbiota and development of vibrio Cholerae specific long term memory b cells in adults after whole cell killed oral Cholera Vaccine
Infection and Immunity, 2021Co-Authors: Denise Chac, Mohammad Murshid Alam, Amit Saha, Taufiqur Rahman Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Umme Salma, Nusrat Jahan, Edward T Ryan, Regina C LarocqueAbstract:Cholera is a diarrheal disease caused by Vibrio Cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. Cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. Cholerae and may be a major determinant of long-term protection from Cholera. Shanchol, a widely used oral Cholera Vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype and OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to Vaccine antigens. Our results suggest that the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential Vaccine adjuvants is warranted.
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anti o specific polysaccharide osp immune responses following vaccination with oral Cholera Vaccine cvd 103 hgr correlate with protection against Cholera after infection with wild type vibrio Cholerae o1 el tor inaba in north american volunteers
PLOS Neglected Tropical Diseases, 2018Co-Authors: Meagan Kelly, Richelle C Charles, Pavol Kovac, Taufiqur Rahman Bhuiyan, Kamrul Islam, Motaher Hossain, Leslie Mayo M Smith, Regina C LarocqueAbstract:Background Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio Cholerae O1 and occasionally O139. A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide (OSP) of V. Cholerae are involved in mediating protection against Cholera. We therefore assessed whether antibody responses against OSP occur after vaccination with live attenuated oral Cholera Vaccine CVD 103-HgR, and whether such responses correlate with protection against Cholera. Methodology We assessed adult North American volunteers (n = 46) who were vaccinated with 5 × 108 colony-forming units (CFU) of oral Cholera Vaccine CVD 103-HgR and then orally challenged with approximately 1 × 105 CFU of wild-type V. Cholerae O1 El Tor Inaba strain N16961, either 10 or 90 days post-vaccination. Principal findings Vaccination was associated with induction of significant serum IgM and IgA anti-OSP and vibriocidal antibody responses within 10 days of vaccination. There was significant correlation between anti-OSP and vibriocidal antibody responses. IgM and IgA anti-OSP responses on day 10 following vaccination were associated with lower post-challenge stool volume (r = −0.44, P = 0.002; r = −0.36, P = 0.01; respectively), and none of 27 Vaccinees who developed a ≥1.5 fold increase in any antibody isotype targeting OSP on day 10 following vaccination compared to baseline developed moderate or severe Cholera following experimental challenge, while 5 of 19 who did not develop such anti-OSP responses did (P = 0.01). Conclusion Oral vaccination with live attenuated Cholera Vaccine CVD 103-HgR induces antibodies that target V. Cholerae OSP, and these anti-OSP responses correlate with protection against diarrhea following experimental challenge with V. Cholerae O1. Trial registration ClinicalTrials.gov NCT01895855
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Protection afforded by oral Cholera Vaccine CVD 103-HgR against diarrhea following subsequent experimental challenge [10].
2018Co-Authors: Kamrul Islam, Meagan Kelly, Richelle C Charles, Pavol Kovac, Taufiqur Rahman Bhuiyan, Regina C Larocque, Motaher Hossain, Leslie Mayo M Smith, Stephen B. CalderwoodAbstract:Protection afforded by oral Cholera Vaccine CVD 103-HgR against diarrhea following subsequent experimental challenge [10].
Ashraful Islam Khan - One of the best experts on this subject based on the ideXlab platform.
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gut microbiota and development of vibrio Cholerae specific long term memory b cells in adults after whole cell killed oral Cholera Vaccine
Infection and Immunity, 2021Co-Authors: Denise Chac, Mohammad Murshid Alam, Amit Saha, Taufiqur Rahman Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Umme Salma, Nusrat Jahan, Edward T Ryan, Regina C LarocqueAbstract:Cholera is a diarrheal disease caused by Vibrio Cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. Cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. Cholerae and may be a major determinant of long-term protection against Cholera. Shanchol, a widely used oral Cholera Vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype or OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower abundance of Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to Vaccine antigens. Our results suggest the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential Vaccine adjuvants is warranted.
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the gut microbiota and development of vibrio Cholerae specific long term memory b cells in adults after whole cell killed oral Cholera Vaccine
Infection and Immunity, 2021Co-Authors: Denise Chac, Mohammad Murshid Alam, Amit Saha, Taufiqur Rahman Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Umme Salma, Nusrat Jahan, Edward T Ryan, Regina C LarocqueAbstract:Cholera is a diarrheal disease caused by Vibrio Cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. Cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. Cholerae and may be a major determinant of long-term protection from Cholera. Shanchol, a widely used oral Cholera Vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype and OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to Vaccine antigens. Our results suggest that the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential Vaccine adjuvants is warranted.
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augmented immune responses to a booster dose of oral Cholera Vaccine in bangladeshi children less than 5 years of age revaccination after an interval of over three years of primary vaccination with a single dose of Vaccine
Vaccine, 2020Co-Authors: Fahima Chowdhury, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Afroza Akter, Imam Tauheed, Saruar Bhuiyan, T Ahmed, Jannatul Ferdous, Pinki Dash, Salima Raiyan BasherAbstract:Abstract We have earlier reported that a single dose of oral Cholera Vaccine (OCV) is protective in adults and children ≥5 years of age and sustained for 2 years. We enrolled participants (n = 240) from this study, between March-September 2017, over 3 years after receiving a primary single dose. Immune responses were measured in placebo group (Primary Immunization group: PI) and compared with those who received a single dose (Booster Immunization group: BI). The children were 4 to 18 years. Blood was collected at day 0 (before vaccination) and after receiving 1st and 2nd doses of OCV. Overall, the BI and PI groups showed vibriocidal antibody response after 1st and 2nd dose of vaccination in all age groups to V. Cholerae O1 and O139. Young children in the BI group showed significantly higher vibriocidal antibody response two weeks after receiving the first dose as compared to PI group to LPS. Elevated plasma IgA responses to LPS after the first dose were observed among the BI group compared to the PI group among the young children. Mucosal antibody responses measured in fecal extracts showed similar increases as that of vibriocidal and LPS responses in the BI group. These results suggest a single boosting dose of OCV generated immune response in primed population >5 years of age who had earlier received OCV. However, young children who had received OCV earlier, boosting after a single dose, resulted in increased immune responses compared to the PI group. Further studies are needed to assess protection obtained from different strategies, especially for young children and to determine the numbers of primary and booster doses needed. In addition, more information is needed regarding the optimum interval between primary and booster doses to plan future interventions for Cholera control. ClinicalTrials.gov Identifier: NCT 02027207.
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Immunogenicity of a killed bivalent whole cell oral Cholera Vaccine in forcibly displaced Myanmar nationals in Cox's Bazar, Bangladesh.
'Public Library of Science (PLoS)', 2020Co-Authors: Fahima Chowdhury, Taufiqur Rahman Bhuiyan, Motaher Hossain, Ashraful Islam Khan, Afroza Akter, Md Saruar Bhuiyan, Imam Tauheed, Tasnuva Ahmed, Shaumik Islam, Tanzeem Ahmed RafiqueAbstract:After the large influx of Rohingya nationals (termed Forcibly Displaced Myanmar National; FDMN) from Rakhine State of Myanmar to Cox's Bazar in Bangladesh, it was apparent that outbreaks of Cholera was very likely in this setting where people were living under adverse water and sanitation conditions. Large campaigns of oral Cholera Vaccine (OCV) were carried out as a preemptive measure to control Cholera epidemics. The aim of the study was to evaluate the immune responses of healthy adults and children after administration of two doses of OCV at 14 days interval in FDMN population and compare with the response observed in Bangladeshi's vaccinated earlier. A cross-sectional immunogenicity study was conducted among FDMNs of three age cohort; in adults (18+years; n = 83), in older children (6-17 years; n = 63) and in younger children (1-5 years; n = 80). Capillary blood was collected at three time points to measure vibriocidal antibodies using either plasma or dried blood spot (DBS) specimens. There was a significant increase of responder frequency of vibriocidal antibody titer at day 14 in all groups for Vibrio Cholerae O1 (Ogawa/Inaba: adults-64%/64%, older children-70%/89% and younger children-51%/75%). There was no overall difference of vibriocidal antibody titer between FDMN and Bangladeshi population at baseline (p = 0.07-0.08) and at day 14, day 28 in all age groups for both serotypes. The seroconversion rate and geometric mean titer (GMT) of either serotype were comparable using both plasma and DBS specimens. These results showed that OCV is capable of inducing robust immune responses in adults and children among the FDMN population which is comparable to that seen in Bangladeshi participants in different age groups or that reported from other Cholera endemic countries. Our results also suggest that the displaced population were exposed to V. Cholerae prior to seeking shelter in Bangladesh
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induction of systemic mucosal and memory antibody responses targeting vibrio Cholerae o1 o specific polysaccharide osp in adults following oral vaccination with an oral killed whole cell Cholera Vaccine in bangladesh
PLOS Neglected Tropical Diseases, 2019Co-Authors: Aklima Akter, Amena Aktar, Sadia Afrin, Fahima Chowdhury, Pinki Dash, Salima Raiyan Basher, Sultana Rownok Jahan, Al Hakim, Asura Khanam Lisa, Ashraful Islam KhanAbstract:Background Oral Cholera Vaccine (OCV) containing killed Vibrio Cholerae O1 and O139 organisms (Bivalent-OCV; Biv-OCV) are playing a central role in global Cholera control strategies. OCV is currently administered in a 2-dose regimen (day 0 and 14). There is a growing body of evidence that immune responses targeting the O-specific polysaccharide (OSP) of V. Cholerae mediate protection against Cholera. There are limited data on anti-OSP responses in recipients of Biv-OCV. We assessed serum antibody responses against O1 OSP, as well as antibody secreting cell (ASC) responses (a surrogate marker for mucosal immunity) and memory B cell responses in blood of adult recipients of Biv-OCV in Dhaka, Bangladesh. Methodology/Principal findings We enrolled 30 healthy adults in this study and administered two doses of OCV (Shanchol) at days 0 and 14. Blood samples were collected before vaccination (day 0) and 7 days after each vaccination (day 7 and day 21), as well as on day 44. Serum responses were largely IgA with minimal IgG and IgM responses in this population. There was no appreciable boosting following day 14 vaccination. There were significant anti-OSP IgA ASC responses on day 7 following the first vaccination, but none after the second immunization. Anti-OSP IgA memory B cell responses were detectable 30 days after completion of the vaccination series, with no evident induction of IgG memory responses. In this population, anti-Ogawa OSP responses were more prominent than anti-Inaba responses, perhaps reflecting impact of previous exposure. Serum anti-OSP responses returned to baseline within 30 days of completing the Vaccine series. Conclusion Our results call into question the utility of the 2-dose regimen separated by 14 days in adults in Cholera endemic areas, and also suggest that Biv-OCV-induced immune responses targeting OSP are largely IgA in this highly endemic Cholera area. Studies in children in Cholera-endemic areas need to be performed. Protective efficacy that extends for more than a month after vaccination presumably is mediated by direct mucosal immune response which is not assessed in this study. Our results suggest a single dose of OCV in adults in a Cholera endemic zone may be sufficient to mediate at least short-term protection.
Taufiqur Rahman Bhuiyan - One of the best experts on this subject based on the ideXlab platform.
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gut microbiota and development of vibrio Cholerae specific long term memory b cells in adults after whole cell killed oral Cholera Vaccine
Infection and Immunity, 2021Co-Authors: Denise Chac, Mohammad Murshid Alam, Amit Saha, Taufiqur Rahman Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Umme Salma, Nusrat Jahan, Edward T Ryan, Regina C LarocqueAbstract:Cholera is a diarrheal disease caused by Vibrio Cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. Cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. Cholerae and may be a major determinant of long-term protection against Cholera. Shanchol, a widely used oral Cholera Vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype or OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower abundance of Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to Vaccine antigens. Our results suggest the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential Vaccine adjuvants is warranted.
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the gut microbiota and development of vibrio Cholerae specific long term memory b cells in adults after whole cell killed oral Cholera Vaccine
Infection and Immunity, 2021Co-Authors: Denise Chac, Mohammad Murshid Alam, Amit Saha, Taufiqur Rahman Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Umme Salma, Nusrat Jahan, Edward T Ryan, Regina C LarocqueAbstract:Cholera is a diarrheal disease caused by Vibrio Cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. Cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. Cholerae and may be a major determinant of long-term protection from Cholera. Shanchol, a widely used oral Cholera Vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype and OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to Vaccine antigens. Our results suggest that the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential Vaccine adjuvants is warranted.
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parenteral vaccination with a Cholera conjugate Vaccine boosts vibriocidal and anti osp responses in mice previously immunized with an oral Cholera Vaccine
American Journal of Tropical Medicine and Hygiene, 2021Co-Authors: Meagan Kelly, Richelle C Charles, Taufiqur Rahman Bhuiyan, Aklima Akter, Stephen B. Calderwood, Jason B Harris, Rajib Biswas, Pavol KovacAbstract:Oral Cholera vaccination protects against Cholera; however, responses in young children are low and of short duration. The best current correlates of protection against Cholera target Vibrio Cholerae O-specific polysaccharide (anti-OSP), including vibriocidal responses. A Cholera conjugate Vaccine has been developed that induces anti-OSP immune responses, including memory B-cell responses. To address whether Cholera conjugate Vaccine would boost immune responses following oral Cholera vaccination, we immunized mice with oral Cholera Vaccine Inaba CVD 103-HgR or buffer only (placebo) on day 0, followed by parenteral boosting immunizations on days 14, 42, and 70 with Cholera conjugate Vaccine Inaba OSP: recombinant tetanus toxoid heavy chain fragment or PBS/placebo. Compared with responses in mice immunized with oral Vaccine alone or intramuscular Cholera conjugate Vaccine alone, mice receiving combination vaccination developed significantly higher vibriocidal, IgM OSP-specific serum responses and OSP-specific IgM memory B-cell responses. A combined vaccination approach, which includes oral Cholera vaccination followed by parenteral Cholera conjugate Vaccine boosting, results in increased immune responses that have been associated with protection against Cholera. These results suggest that such an approach should be evaluated in humans.
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augmented immune responses to a booster dose of oral Cholera Vaccine in bangladeshi children less than 5 years of age revaccination after an interval of over three years of primary vaccination with a single dose of Vaccine
Vaccine, 2020Co-Authors: Fahima Chowdhury, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Afroza Akter, Imam Tauheed, Saruar Bhuiyan, T Ahmed, Jannatul Ferdous, Pinki Dash, Salima Raiyan BasherAbstract:Abstract We have earlier reported that a single dose of oral Cholera Vaccine (OCV) is protective in adults and children ≥5 years of age and sustained for 2 years. We enrolled participants (n = 240) from this study, between March-September 2017, over 3 years after receiving a primary single dose. Immune responses were measured in placebo group (Primary Immunization group: PI) and compared with those who received a single dose (Booster Immunization group: BI). The children were 4 to 18 years. Blood was collected at day 0 (before vaccination) and after receiving 1st and 2nd doses of OCV. Overall, the BI and PI groups showed vibriocidal antibody response after 1st and 2nd dose of vaccination in all age groups to V. Cholerae O1 and O139. Young children in the BI group showed significantly higher vibriocidal antibody response two weeks after receiving the first dose as compared to PI group to LPS. Elevated plasma IgA responses to LPS after the first dose were observed among the BI group compared to the PI group among the young children. Mucosal antibody responses measured in fecal extracts showed similar increases as that of vibriocidal and LPS responses in the BI group. These results suggest a single boosting dose of OCV generated immune response in primed population >5 years of age who had earlier received OCV. However, young children who had received OCV earlier, boosting after a single dose, resulted in increased immune responses compared to the PI group. Further studies are needed to assess protection obtained from different strategies, especially for young children and to determine the numbers of primary and booster doses needed. In addition, more information is needed regarding the optimum interval between primary and booster doses to plan future interventions for Cholera control. ClinicalTrials.gov Identifier: NCT 02027207.
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Immunogenicity of a killed bivalent whole cell oral Cholera Vaccine in forcibly displaced Myanmar nationals in Cox's Bazar, Bangladesh.
'Public Library of Science (PLoS)', 2020Co-Authors: Fahima Chowdhury, Taufiqur Rahman Bhuiyan, Motaher Hossain, Ashraful Islam Khan, Afroza Akter, Md Saruar Bhuiyan, Imam Tauheed, Tasnuva Ahmed, Shaumik Islam, Tanzeem Ahmed RafiqueAbstract:After the large influx of Rohingya nationals (termed Forcibly Displaced Myanmar National; FDMN) from Rakhine State of Myanmar to Cox's Bazar in Bangladesh, it was apparent that outbreaks of Cholera was very likely in this setting where people were living under adverse water and sanitation conditions. Large campaigns of oral Cholera Vaccine (OCV) were carried out as a preemptive measure to control Cholera epidemics. The aim of the study was to evaluate the immune responses of healthy adults and children after administration of two doses of OCV at 14 days interval in FDMN population and compare with the response observed in Bangladeshi's vaccinated earlier. A cross-sectional immunogenicity study was conducted among FDMNs of three age cohort; in adults (18+years; n = 83), in older children (6-17 years; n = 63) and in younger children (1-5 years; n = 80). Capillary blood was collected at three time points to measure vibriocidal antibodies using either plasma or dried blood spot (DBS) specimens. There was a significant increase of responder frequency of vibriocidal antibody titer at day 14 in all groups for Vibrio Cholerae O1 (Ogawa/Inaba: adults-64%/64%, older children-70%/89% and younger children-51%/75%). There was no overall difference of vibriocidal antibody titer between FDMN and Bangladeshi population at baseline (p = 0.07-0.08) and at day 14, day 28 in all age groups for both serotypes. The seroconversion rate and geometric mean titer (GMT) of either serotype were comparable using both plasma and DBS specimens. These results showed that OCV is capable of inducing robust immune responses in adults and children among the FDMN population which is comparable to that seen in Bangladeshi participants in different age groups or that reported from other Cholera endemic countries. Our results also suggest that the displaced population were exposed to V. Cholerae prior to seeking shelter in Bangladesh
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bivalent oral Cholera vaccination induces a memory b cell response to the v Cholerae o1 polysaccharide antigen in haitian adults
PLOS Neglected Tropical Diseases, 2019Co-Authors: Brie Falkard, Wilfredo R Matias, Richelle C Charles, Leslie M Mayosmith, Pavol Kovac, Gregory J Jerome, Edward T Ryan, Evan S Offord, Firdausi QadriAbstract:The bivalent killed whole-cell oral Cholera Vaccine (BivWC) is being increasingly used to prevent Cholera. The presence of O-antigen-specific memory B cells (MBC) has been associated with protective immunity against Cholera, yet MBC responses have not been evaluated after BivWC vaccination. To address this knowledge gap, we measured V. Cholerae O1-antigen MBC responses following BivWC vaccination. Adults in St. Marc, Haiti, received 2 doses of the BivWC Vaccine, Shanchol, two weeks apart. Participants were invited to return at days 7, 21, 44, 90, 180 and 360 after the initial vaccination. Serum antibody and MBC responses were assessed at each time-point before and following vaccination. We observed that vaccination with BivWC resulted in significant O-antigen specific MBC responses to both Ogawa and Inaba serotypes that were detected by day 21 and remained significantly elevated over baseline for up to 12 months following vaccination. The BivWC oral Cholera Vaccine induces durable MBC responses to the V. Cholerae O1-antigen. This suggests that long-term protection observed following vaccination with BivWC could be mediated or maintained by MBC responses.
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Use of oral Cholera Vaccine as a Vaccine probe to determine the burden of culture-negative Cholera.
Public Library of Science (PLoS), 2019Co-Authors: Md Taufiqul Islam, Mohammad Ali, Deok Ryun Kim, Ashraful Islam Khan, Faisal Ahmmed, Yun Chon, K Zaman, Florian Marks, Firdausi QadriAbstract:Analyses of stool from patients with acute watery diarrhea (AWD) using sensitive molecular diagnostics have challenged whether fecal microbiological cultures have acceptably high sensitivity for Cholera diagnosis. If true, these findings imply that current estimates of the global burden of Cholera, which rely largely on culture-confirmation, may be underestimates. We conducted a Vaccine probe study to evaluate this possibility, assessing whether an effective killed oral Cholera Vaccine (OCV) tested in a field trial in a Cholera-endemic population conferred protection against Cholera culture-negative AWD, with the assumption that if cultures are indeed insensitive, OCV protection in such cases should be detectable. We re-analysed the data of a Phase III individually-randomized placebo-controlled efficacy trial of killed OCVs conducted in Matlab, Bangladesh in 1985. We calculated the protective efficacy (PE) of a killed whole cell-only (WC-only) OCV against first-episodes of Cholera culture-negative AWD during two years of post-dosing follow-up. In secondary analyses, we evaluated PE against Cholera culture-negative AWD by age at vaccination, season of onset, and disease severity. In this trial 50,770 people received at least 2 complete doses of either WC-only OCV or placebo, and 791 first episodes of AWD were reported during the follow-up period, of which 365 were culture-positive for Vibrio Cholerae O1. Of the 426 culture-negative AWD episodes, 215 occurred in the WC group and 211 occurred in the placebo group (adjusted PE = -1.7%; 95%CI -23.0 to 13.9%, p = 0.859). No measurable PE of OCV was observed against all or severe Cholera culture-negative AWD when measured overall or by age and season subgroups. In this OCV probe study we detected no Vaccine protection against AWD episodes for which fecal cultures were negative for Vibrio Cholera O1. Results from this setting suggest that fecal cultures from patients with AWD were highly sensitive for Cholera episodes that were etiologically attributable to this pathogen. Similar analyses of other OCV randomized controlled trials are recommended to corroborate these findings
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efficacy of a single dose regimen of inactivated whole cell oral Cholera Vaccine results from 2 years of follow up of a randomised trial
Lancet Infectious Diseases, 2018Co-Authors: Firdausi Qadri, Amit Saha, Thomas F Wierzba, Mohammad Akbar Ali, Fahima Chowdhury, Ashraful Islam Khan, Julia Lynch, Jean Louis Excler, Taufiqul Islam, Yasmin Ara BegumAbstract:Summary Background A single-dose regimen of inactivated whole-cell oral Cholera Vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV Vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up. Methods In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio Cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed Cholera occurring 7–730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207. Findings Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either Vaccine or placebo, of whom 204 700 (102 552 Vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of Cholera (109 among Vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in Vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial Cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in Vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe Cholera was 0·09 (0·07 to 0·12) per 100 000 person-days versus 0·19 (0·15 to 0·23; adjusted protective efficacy 50%, 29 to 65). Vaccine protective efficacy was 52% (8 to 75) against all Cholera episodes and 71% (27 to 88) against severe Cholera episodes in participants aged 5 years to younger than 15 years. For participants aged 15 years or older, Vaccine protective efficacy was 59% (42 to 71) against all Cholera episodes and 59% (35 to 74) against severe Cholera. The protection in the older age groups was sustained throughout the 2-year follow-up. In participants younger than 5 years, the Vaccine did not show protection against either all Cholera episodes (protective efficacy −13%, −68 to 25) or severe Cholera episodes (−44%, −220 to 35). Interpretation A single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group. Funding Bill & Melinda Gates Foundation to the International Vaccine Institute.
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impact of adding hand washing and water disinfection promotion to oral Cholera vaccination on diarrhoea associated hospitalization in dhaka bangladesh evidence from a cluster randomized control trial
International Journal of Epidemiology, 2017Co-Authors: Firdausi Qadri, Nusrat Najnin, Karin Leder, Andrew Forbes, Leanne Unicomb, Peter J Winch, Pavani K Ram, Elli Leontsini, Fosiul A NizameAbstract:Background Information on the impact of hygiene interventions on severe outcomes is limited. As a pre-specified secondary outcome of a cluster-randomized controlled trial among >400 000 low-income residents in Dhaka, Bangladesh, we examined the impact of Cholera vaccination plus a behaviour change intervention on diarrhoea-associated hospitalization. Methods Ninety neighbourhood clusters were randomly allocated into three areas: Cholera-Vaccine-only; Vaccine-plus-behaviour-change (promotion of hand-washing with soap plus drinking water chlorination); and control. Study follow-up continued for 2 years after intervention began. We calculated cluster-adjusted diarrhoea-associated hospitalization rates using data we collected from nearby hospitals, and 6-monthly census data of all trial households. Results A total of 429 995 people contributed 500 700 person-years of data (average follow-up 1.13 years). Vaccine coverage was 58% at the start of analysis but continued to drop due to population migration. In the Vaccine-plus-behaviour-change area, water plus soap was present at 45% of hand-washing stations; 4% of households had detectable chlorine in stored drinking water. Hospitalization rates were similar across the study areas [events/1000 person-years, 95% confidence interval (CI), Cholera-Vaccine-only: 9.4 (95% CI: 8.3-10.6); Vaccine-plus-behaviour-change: 9.6 (95% CI: 8.3-11.1); control: 9.7 (95% CI: 8.3-11.6)]. Cholera cases accounted for 7% of total number of diarrhoea-associated hospitalizations. Conclusions Neither Cholera vaccination alone nor Cholera vaccination combined with behaviour-change intervention efforts measurably reduced diarrhoea-associated hospitalization in this highly mobile population, during a time when Cholera accounted for a small fraction of diarrhoea episodes. Affordable community-level interventions that prevent infection from multiple pathogens by reliably separating faeces from the environment, food and water, with minimal behavioural demands on impoverished communities, remain an important area for research.
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kinetics of antibody secreting cell and fecal iga responses after oral Cholera vaccination in different age groups in a Cholera endemic country
Vaccine, 2017Co-Authors: Marjahan Akhtar, Amit Saha, Ann-mari Svennerholm, Firdausi Qadri, Taufiqur Rahman Bhuiyan, Sarmin Akter, Tanzeem Ahmed Rafique, Arifuzzaman Khan, Laila N Islam, Anna LundgrenAbstract:Immune responses to oral enteric Vaccines in children and infants may be influenced by factors such as age, previous priming with related microorganisms and breast feeding. In this study, we aimed to determine optimal time points to assess immune responses to oral enteric Vaccines in different clinical specimens. This was done by investigating antibody secreting cell (ASC) and fecal antibody responses on different days after vaccination using the licensed oral Cholera Vaccine Dukoral, containing Cholera toxin B-subunit (rCTB) and inactivated Vibrio Cholerae bacteria, as a model Vaccine. Two Vaccine doses were given 2weeks apart to infants (6-11months), young children (12-18months), toddlers (19months-5years) and adults in a Cholera endemic country (Bangladesh). IgA ASC responses, as determined by the antibodies in lymphocyte supernatant (ALS) assay, plasma IgA and IgG responses and secretory IgA (SIgA) responses in extracts of fecal samples were evaluated 4/5 and 7days after each vaccination. After the first Vaccine dose, anti-CTB ALS IgA responses in adults and toddlers were high and comparable on day 5 and 7, while responses were low and infrequent in young children. After the second dose, highest ALS responses were detected on day 5 among the time points studied in all age groups and the responses declined until day 7. In contrast, plasma IgA and IgG anti-CTB responses were high both on day 5 and 7 after the second dose. Fecal SIgA responses in young children and infants were highest on day 7 after the second dose. Our results suggest that ASC/ALS responses to two doses of the oral Cholera Vaccine Dukoral and related oral Vaccines should be analyzed earlier than previously recommended (day 7) at all ages. Fecal antibody responses should preferably be analyzed later than ASC/ALS responses to detect the highest antibody responses.