Enhanced immunogenicity of an oral inactivated cholera vaccine in infants in Bangladesh obtained by zinc supplementation and by temporary withholding breast-feeding

Abstract

The killed oral cholera vaccine Dukoral is recommended for adults and only children over 2 years of age, although cholera is seen frequently in younger children and there is an urgent need for a vaccine for them. Since decreased immunogenicity of oral vaccines in children in developing countries is a critical problem, we tested interventions to enhance responses to Dukoral. We evaluated the effect on the immune responses by temporarily withholding breast-feeding or by giving zinc supplementation. Two doses of Dukoral consisting of killed cholera vibrios and cholera B subunit were given to 6-18 months old Bangladeshi children (n=340) and safety and immunogenicity studied. Our results showed that two doses of the vaccine were safe and induced antibacterial (vibriocidal) antibody responses in 57% and antitoxin responses in 85% of the children. Immune responses were comparable after intake of one and two doses. Temporary withholding breast-feeding for 3 h before immunization or supplementation with 20 mg of zinc per day for 42 days resulted in increased magnitude of vibriocidal antibodies (77% and 79% responders, respectively). Administration of vaccines without buffer or in water did not result in reduction of vibriocidal responses. This study demonstrates that the vaccine is safe and immunogenic in children under 2 years of age and that simple interventions can enhance immune responses in young children.