Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh

Background The mediators of protection against cholera, a severe dehydrating illness of humans caused by Vibrio cholerae, are unknown. We have previously shown that plasma IgA as well as memory B IgG cells targeting lipopolysaccharide (LPS) of Vibrio cholerae O1 correlate with protection against V. cholerae O1 infection among household contacts of cholera patients. Protection against cholera is serogroup specific, and serogroup specificity is defined by the O-specific polysaccharide (OSP) component of LPS. Therefore, we prospectively followed household contacts of cholera patients to determine whether OSP-specific immune responses present at the time of enrollment are associated with protection against V. cholerae infection. Methodology In this study, we enrolled two hundred forty two household contacts of one hundred fifty index patients who were infected with Vibrio cholerae. We determined OSP-specific memory B cells and plasma IgA, IgG and IgM antibody responses on study entry (day 2). Principle findings The presence of OSP-specific plasma IgA, IgM, and IgG antibody responses on study entry were associated with a decrease in the risk of infection in household contacts (IgA, p = 0.015; IgM, p = 0.01, and IgG, p = 0.024). In addition, the presence of OSP-specific IgG memory B cell responses in peripheral blood on study entry was also associated with a decreased risk of infection (44% reduction; 95% CI: 31.1 to 99.8) in contacts. No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cell responses. Conclusion These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. cholerae O1.

[1]  J. Wrammert,et al.  Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells , 2016, mBio.

[2]  S. Afrin,et al.  O-Specific Polysaccharide-Specific Memory B Cell Responses in Young Children, Older Children, and Adults Infected with Vibrio cholerae O1 Ogawa in Bangladesh , 2016, Clinical and Vaccine Immunology.

[3]  T. Sultana,et al.  A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice , 2015, PLoS neglected tropical diseases.

[4]  S. Afrin,et al.  Immune responses to O-specific polysaccharide and lipopolysaccharide of Vibrio cholerae O1 Ogawa in adult Bangladeshi recipients of an oral killed cholera vaccine and comparison to responses in patients with cholera. , 2014, The American journal of tropical medicine and hygiene.

[5]  T. Sultana,et al.  Evaluation in Mice of a Conjugate Vaccine for Cholera Made from Vibrio cholerae O1 (Ogawa) O-Specific Polysaccharide , 2014, PLoS neglected tropical diseases.

[6]  T. Sultana,et al.  Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh , 2013, Clinical and Vaccine Immunology.

[7]  D. Sarracino,et al.  Comparison of Immune Responses to the O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients with Cholera , 2012, Clinical and Vaccine Immunology.

[8]  M. Riyadh,et al.  Memory B Cell Responses to Vibrio cholerae O1 Lipopolysaccharide Are Associated with Protection against Infection from Household Contacts of Patients with Cholera in Bangladesh , 2012, Clinical and Vaccine Immunology.

[9]  M. Riyadh,et al.  Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh , 2012, Clinical and Vaccine Immunology.

[10]  S. Calderwood,et al.  Immune responses to cholera in children , 2012, Expert review of anti-infective therapy.

[11]  S. Calderwood,et al.  Simple, direct conjugation of bacterial O-SP-core antigens to proteins: development of cholera conjugate vaccines. , 2011, Bioconjugate chemistry.

[12]  M. Yunus,et al.  Natural cholera infection-derived immunity in an endemic setting. , 2011, The Journal of infectious diseases.

[13]  M. Riyadh,et al.  Antigen-Specific Memory B-Cell Responses in Bangladeshi Adults after One- or Two-Dose Oral Killed Cholera Vaccination and Comparison with Responses in Patients with Naturally Acquired Cholera , 2011, Clinical and Vaccine Immunology.

[14]  J. Wrammert,et al.  Antigen-Specific Memory B-Cell Responses to Vibrio cholerae O1 Infection in Bangladesh , 2009, Infection and Immunity.

[15]  Firdausi Qadri,et al.  Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh , 2008, PLoS neglected tropical diseases.

[16]  M. Pascual,et al.  Refractory periods and climate forcing in cholera dynamics , 2005, Nature.

[17]  R. Ahmed,et al.  Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system. , 2004, Journal of immunological methods.

[18]  F. Nato,et al.  Preparation, Immunogenicity, and Protective Efficacy, in a Murine Model, of a Conjugate Vaccine Composed of the Polysaccharide Moiety of the Lipopolysaccharide of Vibrio cholerae O139 Bound to Tetanus Toxoid , 2001, Infection and Immunity.

[19]  C. Wennerås,et al.  Lipopolysaccharide- and Cholera Toxin-Specific Subclass Distribution of B-Cell Responses in Cholera , 1999, Clinical Diagnostic Laboratory Immunology.

[20]  C. Wennerås,et al.  Comparison of immune responses in patients infected with Vibrio cholerae O139 and O1 , 1997, Infection and immunity.

[21]  J. Brisson,et al.  Structural analysis of the lipopolysaccharide from Vibrio cholerae O139. , 1996, Carbohydrate Research.

[22]  A. Cox,et al.  Structural analysis of the O-antigen-core region of the lipopolysaccharide from Vibrio cholerae O139. , 1996, Carbohydrate research.

[23]  R. Sack,et al.  Comparison of the vibriocidal antibody response in cholera due to Vibrio cholerae O139 Bengal with the response in cholera due to Vibrio cholerae O1 , 1995, Clinical and diagnostic laboratory immunology.

[24]  F. Mooi,et al.  Genesis of the novel epidemic Vibrio cholerae O139 strain: evidence for horizontal transfer of genes involved in polysaccharide synthesis. , 1995, The EMBO journal.

[25]  D. Maneval,et al.  The capsule and O antigen in Vibrio cholerae O139 Bengal are associated with a genetic region not present in Vibrio cholerae O1 , 1995, Infection and immunity.

[26]  R. Sack,et al.  Lack of cross-protection against diarrhea due to Vibrio cholerae O1 after oral immunization of rabbits with V. cholerae O139 Bengal. , 1994, The Journal of infectious diseases.

[27]  L. Cisneros,et al.  Duration of infection-derived immunity to cholera. , 1981, The Journal of infectious diseases.