Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera

Kaisar, M. Hasanul; Bhuiyan, M. Saruar; Akter, Aklima; Saleem, Danial; Iyer, Anita; Dash, Pinki; Hakim, Al; Chowdhury, Fahima; Khan, Ashraful Islam; Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.; Qadri, Firdausi; Charles, Richelle C.; Bhuiyan, Taufiqur Rahman

doi:10.1128/msphere.01232-20

Cited by 11 publications

(21 citation statements)

References 37 publications

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“…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%

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%

Identifying recent cholera infections using a multiplex bead serological assay

Jones

Bhuiyan

Mills

et al. 2022

Preprint

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“…Systemic, mucosal, and memory B-cells responses to NanH occur after clinical cholera, with NanH found to be the third most common antigenic target of a mucosal homing plasmablast response [ 11 , 17 , 36 ]. NanH is a virulence factor that catalyzes the cleavage of terminal sialic acid residues from gangliosides on the membrane of intestinal epithelial cells to generate monogangliosides (GM1), the binding site for CT [ 37 ].…”

Section: Protein Antigensmentioning

confidence: 99%

“…NanH-neutralizing antibodies have been shown to block the toxin-potentiating effect of NanH in vitro [ 11 ]. These findings together suggest a possible functional role for NanH in protective immunity to cholera and antibody responses to NanH have been found to correlate with protection [ 36 ].…”

Section: Protein Antigensmentioning

confidence: 99%

“…Both adults and children with cholera develop memory B-cells of the IgG and IgA isotypes specific to protein antigens, such as CTB and TcpA, which persist in the circulation out to at least one year following infection. Sialidase-specific IgA memory B-cells have also been demonstrated after cholera [ 36 ]. Similarly, memory B-cells also develop that recognize both LPS and the OSP of V .…”

Section: Correlates Of Protectionmentioning

confidence: 99%

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Systemic, Mucosal, and Memory Immune Responses following Cholera

et al. 2021

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Vibrio cholerae O1, the major causative agent of cholera, remains a significant public health threat. Although there are available vaccines for cholera, the protection provided by killed whole-cell cholera vaccines in young children is poor. An obstacle to the development of improved cholera vaccines is the need for a better understanding of the primary mechanisms of cholera immunity and identification of improved correlates of protection. Considerable progress has been made over the last decade in understanding the adaptive and innate immune responses to cholera disease as well as V. cholerae infection. This review will assess what is currently known about the systemic, mucosal, memory, and innate immune responses to clinical cholera, as well as recent advances in our understanding of the mechanisms and correlates of protection against V. cholerae O1 infection.

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“…Vibriocidal titers remain elevated in the blood for up to a year or longer following infection (Azman et al, 2019), but are not thought to represent a mechanistic form of mucosal immunity (Iyer and Harris, 2021). Serum IgA antibodies specific to several Vibrio cholerae antigens are also correlated with protection from infection (Harris et al, 2008; Kaisar et al, 2021). While intestinal IgA antibodies could represent a direct form of protection, circulating IgA responses are short-lived following V. cholerae infection (Azman et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

A systems serology analysis of correlates of protection against cholera

Wiens

Iyer

Bhuiyan

et al. 2022

Preprint

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Vibriocidal antibodies are the best characterized correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. However, there is no vibriocidal titer threshold associated with absolute protection against infection with Vibrio cholerae or with symptomatic disease in infected individuals. While other circulating antibody responses have also been associated with a decreased risk of V. cholerae infection, there has been no comprehensive comparison of correlates of protection against cholera. To address this, we analyzed 58 serum antibody biomarkers as correlates of protection against both V. cholerae infection and against cholera diarrhea in infected individuals. The study was performed in two cohorts: (1) household contacts of patients with cholera in Bangladesh, and (2) North American volunteers who were vaccinated with a single dose of CVD 103-HgR live oral cholera vaccine and then challenged with virulent V. cholerae O1 El Tor Inaba. In household contacts, we identified 20 antibody markers that were correlated with protection against V. cholerae infection, though there was overlap between distributions. Conditional random forest models identified serum antibody-dependent complement deposition, targeting the V. cholerae O1 antigen, as the most predictive individual correlate of protection from infection, while vibriocidal antibody titers were less predictive. The model that most accurately predicted protection from infection included five biomarkers, with a cross-validated area under the curve (cvAUC) of 79% (95% CI 73-85). Similarly, in North American volunteers who were challenged with V. cholerae after vaccination, a different five-biomarker model predicted protection from the development of cholera diarrhea with a cvAUC of 78% (95% CI 66-91). Thus, while several new biomarkers predict protection better than vibriocidal titers, it remains difficult to consistently predict whether an individual will be protected from future mucosal infection or symptoms using current serologic markers.

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Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera

Abstract: Cholera infection can result in severe dehydration that may lead to death within a short period of time if not treated immediately. Vaccination is an important strategy to prevent the disease.

Cited by 11 publications

References 37 publications

Identifying recent cholera infections using a multiplex bead serological assay

Identifying recent cholera infections using a multiplex bead serological assay

Systemic, Mucosal, and Memory Immune Responses following Cholera

A systems serology analysis of correlates of protection against cholera

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