- Charles, Richelle C;
- Nakajima, Rie;
- Liang, Li;
- Jasinskas, Al;
- Berger, Amanda;
- Leung, Daniel T;
- Kelly, Meagan;
- Xu, Peng;
- Kováč, Pavol;
- Giffen, Samantha R;
- Harbison, James D;
- Chowdhury, Fahima;
- Khan, Ashraful I;
- Calderwood, Stephen B;
- Bhuiyan, Taufiqur Rahman;
- Harris, Jason B;
- Felgner, Philip L;
- Qadri, Firdausi;
- Ryan, Edward T
Background
Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera.Methods
We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V. cholerae O1 in Bangladesh and age-, sex-, and ABO-matched Bangladeshi controls. We validated a subset of identified antigens using enzyme-linked immunosorbent assay.Results
Overall, we identified 608 immunoreactive V. cholerae antigens in our screening, 59 of which had higher immunoreactivity in convalescent compared with acute-stage or healthy control samples (34 in plasma, 39 in mucosal ALS; 13 in both sample sets). Identified antigens included cholera toxin B and A subunits, V. cholerae O-specific polysaccharide and lipopolysaccharide, toxin coregulated pilus A, sialidase, hemolysin A, flagellins (FlaB, FlaC, and FlaD), phosphoenolpyruvate-protein phosphotransferase, and diaminobutyrate-2-oxoglutarate aminotransferase.Conclusions
This study is the first antibody profiling of the mucosal and systemic antibody responses to the nearly complete V. cholerae O1 protein immunome; it has identified antigens that may aid in the development of an improved cholera vaccine.