CD4+ T-cell responses to an oral inactivated cholera vaccine in young children in a cholera endemic country and the enhancing effect of zinc supplementation

Abstract

Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral((R)) containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10-18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P<0.01) and IFN-gamma production (P<0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P>0.05). The IFN-gamma production was significantly higher (P<0.01) but the blast formation comparable (P>0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P<0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-gamma as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.