Dose-dependent circulating immunoglobulin A antibody-secreting cell and serum antibody responses in Swedish volunteers to an oral inactivated enterotoxigenic Escherichia coli vaccine

The immunogenicity of different preparations of an oral inactivated enterot oxigenic Escherichia coli (ETEC) vaccine was evaluated in Swedish volunteer s previously unexposed to ETEC infection. The vaccine prepara tions consist ed of recombinant cholera toxin B subunit (CTB) and various amounts of form alin-killed whole bacteria expressing the most prevalent colonization facto r antigens (CFAs). Significant immunoglobulin A (IgA) antibody-secreting ce ll (ASC) responses against CTB and the various CFA components were seen in a majority of volunteers after two doses of ETEC vaccine independent of the vaccine lot given. The IgA ASC responses against CTB were significantly hi gher after the second than after the first immunization, whereas the CFA-sp ecific IgA ASC responses were almost comparable after the first and second doses of ETEC vaccine. Two immunizations with one-third of a full dose of C FA-ETEC bacteria induced lower frequencies of IgA ASC responses against all the different CFAs than two full vaccine doses, i,e., 63 versus 80% for CF A/I, 56 versus 70% for CS1, 31 versus 65% for CS2, and 56 versus 75% for CS 4. The proportion of vaccinees responding with rises in the titer of serum IgA antibody against the various CFA antigens was also lower after immuniza tion with the reduced dose of CFA-ETEC bacteria. These findings suggest tha t measurements of circulating IgA ASCs can be used not only for qualitative but also for quantitative assessments of the immunogenicity of individual fimbrial antigens in various preparations of ETEC vaccine.