Cholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants.

Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children.

The Fatal Clinical Outcome of Severe COVID-19 in Hospitalized Patients: Findings from a Prospective Cohort Study in Dhaka, Bangladesh.

Background and Objectives: The morbidity and mortality associated with COVID-19 have burdened worldwide healthcare systems beyond their capacities, forcing them to promptly investigate the virus characteristics and its associated outcomes. This clinical analysis aimed to explore the key factors related to the fatal outcome of severe COVID-19 cases. Materials and Methods: Thirty-five adult severe COVID-19 patients were enrolled from two COVID-19 hospitals in Dhaka, Bangladesh. Clinical manifestation, comorbid conditions, medications, SARS-CoV-2 RT-PCR related cycle threshold (CT) value, hematology, biochemical parameters with SARS-CoV-2 specific IgG and IgM responses at enrollment were compared between the survivors and deceased participants. Results: Total 27 patients survived and 8 patients died within 3 months of disease onset. Deceased patients suffered longer from shortness of breath than the survived (p = 0.049). Among the severe cases, 62% of the deceased patients had multiple comorbid condition compared to 48% of those who survived. Interestingly, the anti-viral was initiated earlier among the deceased patients [median day of 1 (IQR: 0, 1.5) versus 6.5 (IQR: 6.25, 6.75)]. Most of the survivors (55%) received a combination of anticoagulant (p = 0.034). Liver enzymes, creatinine kinase, and procalcitonin were higher among the deceased patients during enrollment. The median CT value among the deceased was significantly lower than the survivors (p = 0.025). A significant difference for initial IgG (p = 0.013) and IgM (p = 0.030) responses was found between the survivor and the deceased groups. Conclusions: The factors including older age, male gender, early onset of respiratory distress, multiple comorbidities, low CT value, and poor antibody response may contribute to the fatal outcome in severe COVID-19 patients. Early initiation of anti-viral and a combination of anticoagulant treatment may prevent or lower the fatality among severe COVID-19 cases.

Determining clinical biomarkers to predict long-term SARS-CoV-2 antibody response among COVID-19 patients in Bangladesh.

Background: Information on antibody responses following SARS-CoV-2 infection, including the magnitude and duration of responses, is limited. In this analysis, we aimed to identify clinical biomarkers that can predict long-term antibody responses following natural SARS-CoV-2 infection. Methodology: In this prospective study, we enrolled 100 COVID-19 patients between November 2020 and February 2021 and followed them for 6 months. The association of clinical laboratory parameters on enrollment, including lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), ferritin, procalcitonin (PCT), and D-dimer, with predicting the geometric mean (GM) concentration of SARS-CoV-2 receptor-binding domain (RBD)-specific IgG antibody at 3 and 6 months post-infection was assessed in multivariable linear regression models. Result: The mean ± SD age of patients in the cohort was 46.8 ± 14 years, and 58.8% were male. Data from 68 patients at 3 months follow-up and 55 patients at 6 months follow-up were analyzed. Over 90% of patients were seropositive against RBD-specific IgG till 6 months post-infection. At 3 months, for any 10% increase in absolute lymphocyte count and NLR, there was a 6.28% (95% CI: 9.68, -2.77) decrease and 4.93% (95% CI: 2.43, 7.50) increase, respectively, in GM of IgG concentration, while any 10% increase for LDH, CRP, ferritin, and procalcitonin was associated with a 10.63, 2.87, 2.54, and 3.11% increase in the GM of IgG concentration, respectively. Any 10% increase in LDH, CRP, and ferritin was similarly associated with an 11.28, 2.48, and 3.0% increase in GM of IgG concentration at 6 months post-infection. Conclusion: Several clinical biomarkers in the acute phase of SARS-CoV-2 infection are associated with enhanced IgG antibody response detected after 6 months of disease onset. The measurement of SARS-CoV-2 specific antibody responses requires improved techniques and is not feasible in all settings. Baseline clinical biomarkers can be a useful alternative as they can predict antibody response during the convalescence period. Individuals with an increased level of NLR, CRP, LDH, ferritin, and procalcitonin may benefit from the boosting effect of vaccines. Further analyses will determine whether biochemical parameters can predict RBD-specific IgG antibody responses at later time points and the association of neutralizing antibody responses.

A snap-shot of a diarrheal epidemic in Dhaka due to enterotoxigenic Escherichia coli and Vibrio cholerae O1 in 2022.

Background: Enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae O1 are most common bacterial causes of diarrheal diseases in Bangladesh. This analysis projected distribution of ETEC and V. cholerae O1 among diarrheal patients of icddr,b, Dhaka hospital in two diarrheal peaks of 2022. Methodology: Under the 2% systematic surveillance system, stool samples collected from diarrheal patients of icddr,b hospital were cultured and diagnostic testing was done for ETEC and V. cholerae O1. Comparison of positive cases was done between first peak (March-April) and second peak (October-November) in 2022. Results: A total of 2,937 stool specimens were tested of which 12% were ETEC and 20% were V. cholerae O1. About 40% of the severe dehydration cases were infected with V. cholerae O1. Predominant ETEC enterotoxin type was 'LT/ST' (41%). The LT enterotoxin significantly increased from 13% to 28% in the second peak (p = 0.015). The predominant colonization factors (CFs) on ETEC were CS5 + CS6 (23%), followed by CS6 (15%). CF-positive isolates was significantly higher in the second peak (36%) than in the first peak (22%) (p = 0.043). Total 14% cases were co-infected with ETEC and V. cholerae O1. Significant differences in the distribution of enterotoxin types were observed (p = 0.029) among the co-infection cases. Conclusion: Changing patterns of enterotoxin and CFs observed in ETEC pathogens should be taken into consideration for ETEC vaccine development. Considering cholera and ETEC biannual trends in causing diarrheal epidemics and outbreaks, emphasizes the need for thoughts on combination vaccine strategies for preventing acute watery diarrhea due to the two major bacterial pathogens.

Appearance of tolerance-induction and non-inflammatory SARS-CoV-2 spike-specific IgG4 antibodies after COVID-19 booster vaccinations.

Background: Understanding the characteristics of the humoral immune responses following COVID-19 vaccinations is crucial for refining vaccination strategies and predicting immune responses to emerging SARS-CoV-2 variants. Methods: A longitudinal analysis of SARS-CoV-2 spike receptor binding domain (RBD) specific IgG antibody responses, encompassing IgG subclasses IgG1, IgG2, IgG3, and IgG4 was performed. Participants received four mRNA vaccine doses (group 1; n=10) or two ChAdOx1 nCoV-19 and two mRNA booster doses (group 2; n=19) in Bangladesh over two years. Results: Findings demonstrate robust IgG responses after primary Covishield or mRNA doses; declining to baseline within six months. First mRNA booster restored and surpassed primary IgG responses but waned after six months. Surprisingly, a second mRNA booster did not increase IgG levels further. Comprehensive IgG subclass analysis showed primary Covishield/mRNA vaccination generated predominantly IgG1 responses with limited IgG2/IgG3, Remarkably, IgG4 responses exhibited a distinct pattern. IgG4 remained undetectable initially but increased extensively six months after the second mRNA dose, eventually replacing IgG1 after the 3rd/4th mRNA doses. Conversely, initial Covishield recipients lack IgG4, surged post-second mRNA booster. Notably, mRNA-vaccinated individuals displayed earlier, robust IgG4 levels post first mRNA booster versus Covishield counterparts. IgG1 to IgG4 ratios decreased with increasing doses, most pronounced with four mRNA doses. This study highlights IgG response kinetics, influenced by vaccine type and doses, impacting immunological tolerance and IgG4 induction, shaping future vaccination strategies. Conclusions: This study highlights the dynamics of IgG responses dependent on vaccine type and number of doses, leading to immunological tolerance and IgG4 induction, and shaping future vaccination strategies.

Measuring the Effectiveness of COVID-19 Vaccines Used during a Surge of the Delta Variant of SARS-CoV-2 in Bangladesh: A Test-Negative Design Evaluation.

BACKGROUND: From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant. METHODS: A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days' duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose. RESULTS: In total, 313 cases were matched to 1196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: -21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines. CONCLUSIONS: Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries.

Longevity of memory B cells and antibodies, as well as the polarization of effector memory helper T cells, are associated with disease severity in patients with COVID-19 in Bangladesh.

The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets.

Correlation of antigen-specific immune response with disease severity among COVID-19 patients in Bangladesh.

Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM+ (both OX40+CD137+ and OX40+CD40L+) CD4+ T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIMs (CD137+CD69+), which indicates the exhaustion of CD8+ T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2.

Disease characteristics and serological responses in patients with differing severity of COVID-19 infection: A longitudinal cohort study in Dhaka, Bangladesh.

BACKGROUND: COVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients. METHODOLOGY/PRINCIPAL FINDINGS: This longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases. Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases. CONCLUSION/SIGNIFICANCE: We report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.

A non-inferiority trial comparing two killed, whole cell, oral cholera vaccines (Cholvax vs. Shanchol) in Dhaka, Bangladesh.

Bangladesh remains cholera endemic with biannual seasonal peaks causing epidemics. At least 300,000 severe cases and over 4,500 deaths occur each year. The available oral cholera vaccineshave not yet been adopted for cholera control in Bangladesh due to insufficient number of doses available for endemic control. With a public private partnership, icddr,b initiated a collaboration between vaccine manufacturers in Bangladesh and abroad. A locally manufactured Oral Cholera Vaccine (OCV) named Cholvax became available for testing in Bangladesh. We evaluated the safety and immunogenicity of this locally produced Cholvax (Incepta Vaccine Ltd) inexpensive OCV comparatively to Shanchol (Shantha Biotechnics-Sanofi Pasteur) which is licensed in several countries. We conducted a randomized non-inferiority clinical trial of bivalent, killed oral whole-cell cholera vaccine Cholvax vs. Shanchol in the cholera-endemic area of Mirpur, Dhaka, among three different age cohorts (1-5, 6-17 and 18-45 years) between April 2016 and April 2017. Two vaccine doses were given at 14 days apart to 2,052 healthy participants. No vaccine-related serious adverse events were reported. There were no significant differences in the frequency of solicited (7.31% vs. 6.73%) and unsolicited (1.46% vs. 1.07%) adverse events reported between the Cholvax and Shanchol groups. Vibriocidal antibody responses among the overall population for O1 Ogawa (81% vs. 77%) and O1 Inaba (83% vs. 84%) serotypes showed that Cholvax was non-inferior to Shanchol, with the non-inferiority margin of -10%. For O1 Inaba, GMT was 462.60 (Test group), 450.84 (Comparator group) with GMR 1.02(95% CI: 0.92, 1.13). For O1 Ogawa, GMT was 419.64 (Test group), 387.22 (Comparator group) with GMR 1.12 (95% CI: 1.02, 1.23). Cholvax was safe and non-inferior to Shanchol in terms of immunogenicity in the different age groups. These results support public use of Cholvax to contribute for reduction of the cholera burden in Bangladesh. ClinicalTrials.gov number: NCT027425581.

Long-term sialidase-specific immune responses after natural infection with cholera: Findings from a longitudinal cohort study in Bangladesh.

Background: Immune responses that target sialidase occur following natural cholera and have been associated with protection against cholera. Sialidase is a neuraminidase that facilitates the binding of cholera toxin (CT) to intestinal epithelial cells. Despite this, little is known about age-related sialidase-specific immune responses and the impact of nutritional status and co-infection on sialidase-specific immunity. Methods: We enrolled 50 culture-confirmed Vibrio cholerae O1 cholera cases presenting to the icddr,b Dhaka hospital with moderate to severe dehydration. We evaluated antibody responses out to 18 months (day 540) following cholera. We assessed immune responses targeting sialidase, lipopolysaccharide (LPS), cholera toxin B subunit (CtxB), and vibriocidal responses. We also explored the association of sialidase-specific immune responses to nutritional parameters and parasitic co-infection of cases. Results: This longitudinal cohort study showed age-dependent differences in anti-sialidase immune response after natural cholera infection. Adult patients developed plasma anti-sialidase IgA and IgG responses after acute infection (P<0.05), which gradually decreased from day 30 on. In children, no significant anti-sialidase IgA, IgM, and IgG response was seen with the exception of a late IgG response at study day 540 (p=0.05 compared to adults). There was a correlation between anti-sialidase IgA with vibriocidal titers, as well as anti-sialidase IgA and IgG with anti-LPS and anti-CtxB antibody responses in adult patients, whereas in children, a significant positive correlation was seen only between anti-sialidase IgA and CtxB IgA responses. Stunted children showed significantly lower anti-sialidase IgA, IgG, and IgM antibody responses and higher LPS IgG and IgM antibody responses than healthy children. The anti-sialidase IgA and IgG responses were significantly higher in cases with concomitant parasitic infection. Conclusion: Our data suggest that cholera patients develop age-distinct systemic and mucosal immune responses against sialidase. The stunted children have a lower anti-sialidase antibody response which may be associated with gut enteropathy and the neuraminidase plays an important role in augmented immune response in cholera patients infected with parasites.

A non-inferiority trial comparing two recombinant vaccines (Hepa-B vs. Engerix-B) for hepatitis B among adults in Dhaka, Bangladesh.

Worldwide Hepatitis B is known as one of the imperative causes of mortality and morbidity as well as occupational health hazard among health workers. Bangladesh is intermediate endemic country for Hepatitis B infection for which the government has introduced hepatitis B vaccination into the Expanded Programme on Immunization (EPI) nationwide since 2009 for new born children. However, the people who were born before 2009, was dependent on imported hepatitis B vaccine as there was no locally manufactured hepatitis B vaccine in Bangladesh. Hence, we conducted a randomized observer blinded non-inferiority clinical trial to assess the immunogenicity and safety of the locally manufactured Hepa-B vaccine in comparison with World Health Organization prequalified Engerix-B vaccine. Total 158 eligible adult participants were enrolled in this study with mean age of 30 and 29 years old in Hepa-B and Engerix-B groups, respectively. Both the vaccines were administered intramuscularly at 0, 1 and 6 months schedule. Baseline and post vaccination anti-HBs titers were measure at different time points. Seroconversion rate post three doses of Hepa-B vaccine was 98.67% similar to the comparator Engerix-B vaccine which was 100%. The geometric mean test ratios of both vaccines at all analysis time points were found > 0.5 predefined non-inferiority margin. Soreness at the injection site was the most common symptom for both the vaccines which resolved without any complication. No serious adverse event was reported throughout the study period. These results suggest that locally manufactured hepatitis B vaccine 'Hepa-B' vaccine is non-inferior to the well-known licensed 'Engerix-B' vaccine. ClinicalTrials.gov NCT03627507.

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.

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.

Immunogenicity of a killed bivalent whole cell oral cholera vaccine in forcibly displaced Myanmar nationals in Cox's Bazar, Bangladesh.

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.

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.

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 <5 years, 5 to <18 years and adults >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: NCT02027207.