Antibody-secreting cells in human peripheral blood after oral immunization with an inactivated enterotoxigenic Escherichia coli vaccine.
Vaccine antigen-specific antibody-secreting cell (ASC) responses in peripheral blood of healthy adult volunteers were studied after oral immunization with a prototype enterotoxigenic Escherichia coli (ETEC) vaccine by means of the enzyme-linked immunospot technique. Three doses of vaccine consisting of formalin-killed ETEC bacteria expressing fimbrial colonization factor antigens I and II (CFA/I and CFA/II) in combination with purified cholera toxin B subunit (CTB) were given 2 weeks apart. The ASC responses were detected 7 days after each immunization. Immunoglobulin A (IgA) was the predominant isotype produced by CFA/I- as well as CFA/II-specific ASCs. Moderate CFA/I- and CFA/II-specific IgM-secreting ASC (IgM-ASC) responses were also seen, whereas IgG-ASC responses to either of the CFAs were negligible. The ASC responses to CTB, on the other hand, comprised both IgA- and IgG-ASCs, with few if any specific IgM-ASCs. Almost 90% of the volunteers developed CFA-specific ASC responses after vaccination. Maximal CFA-specific ASC responses were usually observed after a single dose or two doses of vaccine. A third dose of vaccine did not result in increased but rather resulted in decreased magnitudes of CFA-specific ASC responses. Furthermore, it was found that CTB did not function as a mucosal adjuvant, since CFA-specific ASC responses were not enhanced by the simultaneous administration of CTB. These results suggest that two oral doses of ETEC vaccine induce a strong mucosal immune response, as reflected by the presence of large numbers of antigen-specific mucosal B cell immunoblasts in the blood.
Wennerås
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Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Svennerholm
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Ahrén
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Czerkinsky
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D000284:Administration, Oral; D000328:Adult; D000917:Antibody Formation; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology; D003967:Diarrhea / Q000517:prevention & control; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D036781:Fimbriae Proteins; D006801:Humans; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D015164:Vaccines, Inactivated
D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015164:Vaccines, Inactivated; C022924:colonization factor antigens; D036781:Fimbriae Proteins; D002772:Cholera Toxin