Defining Polysaccharide-Specific Antibody Targets against Vibrio cholerae O139 in Humans following O139 Cholera and following Vaccination with a Commercial Bivalent Oral Cholera Vaccine, and Evaluation of Conjugate Vaccines Targeting O139

Kamruzzaman, Mohammad; Kelly, Meagan; Charles, Richelle C.; Harris, Jason B.; Calderwood, Stephen B.; Akter, Aklima; Biswas, Rajib; Kaisar, M. Hasanul; Bhuiyan, Taufiqur Rahman; Ivers, Louise C; Ternier, Ralph; Jerome, J. Gregory; Pfister, Hélène B.; Lu, Xinmin; Soliman, Sameh E.; Ruttens, Bart; Saksena, Rina; Mečárová, Jana; Čížová, Alžbeta; Qadri, Firdausi; Bystrický, Slavomı́r; Kòváč, Pavol; Xu, Peng; Ryan, Edward T.

doi:10.1128/msphere.00114-21

Cited by 3 publications

(11 citation statements)

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“…Antigens were produced as previously described [33][34][35][36][37][38], or purchased from a commercial source, and are described in detail in the testing protocol. OSP antigens were produced as OSP:BSA (bovine serum albumin) conjugates to facilitate binding to the polysterene beads [33][34][35]. All antigens were conjugated to Luminex magnetic beads using carbodiimide coupling according to the manufacturer's recommendations.…”

Section: Serological Testing and Data Processingmentioning

confidence: 99%

“…Additionally, O139 serogroup OSP (V. cholerae O139 serogroup is rarely detected as circulating in the last decade, but is included in the most commonly used oral cholera vaccines), heat labile enterotoxin subunit B (LT-B), and heat labile holo-enterotoxin (LT-H) (expressed during infection with enterotoxigenic Escherichia coli [ETEC] and have a high degree of homology with cholera toxin counterparts) and influenza haemaglutinin 1 (Flu) (as a control antigen) were also selected. Antigens were produced as previously described [33][34][35][36][37][38], or purchased from a commercial source, and are described in detail in the testing protocol. OSP antigens were produced as OSP:BSA (bovine serum albumin) conjugates to facilitate binding to the polysterene beads [33][34][35].…”

Section: Serological Testing and Data Processingmentioning

confidence: 99%

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Identifying recent cholera infections using a multiplex bead serological assay

Jones

Bhuiyan

Mills

et al. 2022

Preprint

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Background: Estimates of incidence based on medically attended cholera can be severely biased. Vibrio cholerae O1 leaves a lasting antibody signal and recent advances show that these can be used to estimate infection incidence rates from cross-sectional serologic data. Current laboratory methods are resource intensive and challenging to standardize across laboratories. A multiplex bead assay (MBA) could efficiently expand the breadth of measured antibody responses and improve seroincidence accuracy. Methods: We tested 305 serum samples from confirmed cholera cases (4-1083d post-infection) and uninfected contacts in Bangladesh using an MBA (IgG/IgA/IgM for 7 Vibrio cholerae O1-specific antigens) as well as traditional vibriocidal and enzyme-linked immunosorbent assays (2 antigens, IgG and IgA). Results: While post-infection vibriocidal responses were larger than other markers, several MBA-measured antibodies demonstrated robust responses with similar half-lives. Random forest models combining all MBA antibody measures allowed for accurate identification of recent cholera infections (e.g. past 200 days) including a cross-validated AUC (cvAUC200) of 92% with simpler 3 IgG antibody models having similar accuracy. Across infection windows between 45- and 300-days, accuracy of models trained on MBA measurements were non-inferior to models based on traditional assays. Conclusions: Our results illustrate a scalable cholera serosurveillance tool that can be incorporated into multi-pathogen serosurveillance platforms.

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Section: Serological Testing and Data Processingmentioning

confidence: 99%

Section: Serological Testing and Data Processingmentioning

confidence: 99%

Identifying recent cholera infections using a multiplex bead serological assay

Jones

Bhuiyan

Mills

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, O139 serogroup OSP ( V. cholerae O139 serogroup has been rarely detected as circulating in the last decade, but is included in the most commonly used oral cholera vaccines), heat-labile enterotoxin subunit B (LT-B), and heat-labile holo-enterotoxin (LT-H) (expressed during infection with enterotoxigenic Escherichia coli [ETEC] and have a high degree of homology with cholera toxin counterparts) and influenza hemaglutinin 1 (flu) (as a control antigen) were also selected. Antigens were produced as previously described ( 29 , 30 , 40 – 43 ), or purchased from a commercial source, and are described in detail in the testing protocol. OSP antigens were produced as OSP:BSA (bovine serum albumin) conjugates to facilitate binding to the polystyrene beads ( 40 – 42 ).…”

Section: Methodsmentioning

confidence: 99%

“…Antigens were produced as previously described ( 29 , 30 , 40 – 43 ), or purchased from a commercial source, and are described in detail in the testing protocol. OSP antigens were produced as OSP:BSA (bovine serum albumin) conjugates to facilitate binding to the polystyrene beads ( 40 – 42 ). All antigens were conjugated to Luminex magnetic beads using carbodiimide coupling according to the manufacturer’s recommendations.…”

Section: Methodsmentioning

confidence: 99%

Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay

Jones

Bhuiyan

Muise

et al. 2022

mBio

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“…Furthermore, V. cholerae O139 expresses a capsule comprised of a polymer of the OSP-hexasaccharide ( 15 , 18 – 21 ), while V. cholerae O1 is unencapsulated. We have previously characterized the immune response to O139 OSP and its fragments using pooled human patient serum samples and found that the terminal tetrasaccharide of the OSP-hexasaccharide is particularly immunogenic ( 22 ). Despite the importance of OSP-specific responses in mediating protection against cholera caused by V. cholerae O1 ( 23 ), little is known about OSP-specific responses in individual patients infected with V. cholerae O139 and in vaccine recipients of bivalent (O1/O139) oral killed cholera vaccine (OCV) currently included in the global stockpile of cholera vaccine and used in cholera control programs.…”

Section: Introductionmentioning

confidence: 99%

Comparison of O-specific polysaccharide responses in patients following infection with Vibrio cholerae O139 versus vaccination with a bivalent (O1/O139) oral killed cholera vaccine in Bangladesh

Kaisar,

Kelly,

Kamruzzaman

et al. 2023

mSphere

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Cholera caused by Vibrio cholerae O139 emerged in the early 1990s and spread rapidly to 11 Asian countries before receding for unclear reasons. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). V. cholerae O139 also expresses the OSP-capsule. We, therefore, assessed antibody responses targeting V. cholerae O139 OSP, LPS, capsule, and vibriocidal responses in patients in Bangladesh with cholera caused by V. cholerae O139. We compared these responses to those of age-gender-blood group-matched recipients of the bivalent oral cholera vaccine (OCV O1/O139). We found prominent OSP, LPS, and vibriocidal responses in patients, with a high correlation between these responses. OSP responses primarily targeted the terminal tetrasaccharide of OSP. Vaccinees developed OSP, LPS, and vibriocidal antibody responses, but of significantly lower magnitude and responder frequency (RF) than matched patients. We separately analyzed responses in pediatric vaccinees born after V. cholerae O139 had receded in Bangladesh. We found that OSP responses were boosted in children who had previously received a single dose of bivalent OCV 3 yr previously but not in vaccinated immunologically naïve children. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 despite the presence of capsules, that vaccination with bivalent OCV is poorly immunogenic in the short term in immunologically naïve individuals, but that OSP-specific immune responses can be primed by previous exposure, although whether such responses can protect against O139 cholera is uncertain. IMPORTANCE Cholera is a severe dehydrating illness in humans caused by Vibrio cholerae serogroups O1 or O139. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) of V. cholerae LPS. Yet, little is known about immunity to O139 OSP. In this study, we assessed immune responses targeting OSP in patients from an endemic region with cholera caused by V. cholerae O139. We compared these responses to those of the age-gender-blood group-matched recipients of the bivalent oral cholera vaccine. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 and that the OSP responses primarily target the terminal tetrasaccharide of OSP. Our results further suggest that vaccination with the bivalent vaccine is poorly immunogenic in the short term for inducing O139-specific OSP responses in immunologically naïve individuals, but OSP-specific immune responses can be primed by previous exposure or vaccination.

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Defining Polysaccharide-Specific Antibody Targets against Vibrio cholerae O139 in Humans following O139 Cholera and following Vaccination with a Commercial Bivalent Oral Cholera Vaccine, and Evaluation of Conjugate Vaccines Targeting O139

Abstract: Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae serogroup O1 or O139. Protection against cholera is serogroup specific, and serogroup specificity is defined by O-specific polysaccharide (OSP).

Cited by 3 publications

References 64 publications

Identifying recent cholera infections using a multiplex bead serological assay

Identifying recent cholera infections using a multiplex bead serological assay

Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay

Comparison of O-specific polysaccharide responses in patients following infection with Vibrio cholerae O139 versus vaccination with a bivalent (O1/O139) oral killed cholera vaccine in Bangladesh

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