Intestinal and systemic immune responses in humans after oral immunization with a bivalent B subunit-O1/O139 whole cell cholera vaccine.

There is a need for an effective vaccine that can protect against cholera caused by either Vibrio cholerae O1 or by the new pandemic serotype O139 Bengal. An oral bivalent B subunit-O1/O139 whole cell (B-O1/O139 WC) cholera vaccine has been prepared by adding formalin-killed O139 vibrios to the recently licensed oral recombinant B-O1 WC vaccine. When tested in Swedish volunteers, this B-O1/O139 WC vaccine was found to be safe and immunogenic. Two vaccine doses given 2 weeks apart induced statistically significant, P < 0.05, mucosal IgA antibody responses in intestinal lavage fluid against cholera toxin in all of nine vaccinees and against both O1 and O139 vibrios in seven of nine cases. The intestinal responses were associated with similar high frequencies of intestine-derived antibody-secreting cell responses in peripheral blood to the different antigens. A third dose of vaccine given after 5-6 weeks did not result in any further increased response. All of 12 vaccinees responded with significant IgA and IgG antitoxin responses in serum associated with significant vibriocidal antibody titre rises against O1 vibrios in 10 cases (83%) and against O139 vibrios in eight vaccinees (67%). The frequencies and magnitudes of the serological responses to the B subunit and O1 WC components were similar to those induced by the B-O1 WC vaccine. Thus, the O139 component of the vaccine induced intestinal and systemic antibacterial immune responses in the majority of the vaccinees, and its addition to the vaccine did not interfere with the immunogenicity of the B subunit or O1 WC components.