title: Antigen-specific memory T cell responses after vaccination with an oral killed cholera vaccine in Bangladeshi children and comparison to responses in patients with naturally acquired cholera.
abstract: Young children, older children, and adults develop comparable levels and durations of immunity following cholera. In comparison, young children receiving oral killed cholera vaccines (OCV) develop a lower level and shorter duration of protection than those of older children and adults. The reasons for this are unclear. We investigated OCV-induced memory T cell responses in younger and older children and compared responses to those in children with cholera. We found that patients with cholera developed significant levels of toxin-specific effector memory T cells (T(EM)) with follicular helper and gut-homing characteristics. Older children (6 to 14 years of age) receiving two doses of OCV containing recombinant cholera toxin B subunit (rCTB) had more modest T(EM) responses with follicular helper and gut-homing characteristics, but younger vaccinees (24 to 71 months of age) did not develop T(EM) responses. The T(EM) response correlated positively with subsequent IgG memory B cell responses specific to rCTB in older vaccinees. Cytokine analyses indicated that cholera patients developed significant Th1, Th17, and Th2 responses, while older children receiving vaccine developed more modest increases in Th1 and Th17 cells. Younger vaccinees had no increase in Th1 cells, a decrease in Th17 cells, and an increase in regulatory T (Treg) cells. Our findings suggest that T cell memory responses are markedly diminished in children receiving OCV, especially young children, compared to responses following naturally acquired cholera, and that these differences affect subsequent development of memory B cell responses. These findings may explain the lower efficacy and shorter duration of protection afforded by OCV in young children.
authors: Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.
authors: Mohammad
authors: M
authors: Arifuzzaman
authors: Rasheduzzaman
authors: R
authors: Rashu
authors: Daniel T
authors: DT
authors: Leung
authors: M Ismail
authors: MI
authors: Hosen
authors: Taufiqur Rahman
authors: TR
authors: Bhuiyan
authors: M Saruar
authors: MS
authors: Bhuiyan
authors: Mohammad Arif
authors: MA
authors: Rahman
authors: Farhana
authors: F
authors: Khanam
authors: Amit
authors: A
authors: Saha
authors: Richelle C
authors: RC
authors: Charles
authors: Regina C
authors: RC
authors: LaRocque
authors: Ana A
authors: AA
authors: Weil
authors: John D
authors: JD
authors: Clements
authors: Randall K
authors: RK
authors: Holmes
authors: Stephen B
authors: SB
authors: Calderwood
authors: Jason B
authors: JB
authors: Harris
authors: Edward T
authors: ET
authors: Ryan
authors: Firdausi
authors: F
authors: Qadri
mesh_terms: D000293:Adolescent; D000328:Adult; D000992:Antitoxins / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D001459:Bangladesh; D002648:Child; D002675:Child, Preschool; D002771:Cholera / Q000276:immunology* / Q000517:prevention & control; D002772:Cholera Toxin / Q000276:immunology; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D000992:Antitoxins; D022121:Cholera Vaccines; D016207:Cytokines; D007074:Immunoglobulin G; D015164:Vaccines, Inactivated; D002772:Cholera Toxin