title: Mucosal immunization with Vibrio cholerae outer membrane vesicles provides maternal protection mediated by antilipopolysaccharide antibodies that inhibit bacterial motility.
abstract: Vibrio cholerae is the causative agent of cholera, a severe diarrheal disease that remains endemic in many parts of the world and can cause outbreaks wherever sanitation and clean water systems break down. Prevention of disease could be achieved through improved sanitation and clean water provision supported by vaccination. V. cholerae serogroup O1 is the major cause of cholera; O1 serotypes Inaba and Ogawa have similar disease burdens, while O139 is the only non-O1 serogroup to cause epidemics. We showed previously that immunization of adult female mice with purified V. cholerae outer membrane vesicles (OMVs) elicits an antibody response that protect neonates from oral V. cholerae challenge and that suckling from an immunized dam accounts for the majority of protection from V. cholerae colonization. Here we report that lipopolysaccharide (LPS) is the major OMV protective antigen. Mucosal immunization with OMVs from Inaba or Ogawa provides significant cross-serotype protection from V. cholerae colonization, although serotype-specific antigens are dominant. OMVs from O1 or O139 do not provide cross-serogroup protection, but by immunization with a mixture of O1 and O139 OMVs, cross-serogroup protection was achieved. Neonatal protection is not associated with significant bacterial death but may involve inhibition of motility, as antibodies from OMV-immunized mice inhibit V. cholerae motility in vitro, with trends that parallel in vivo protection. Motility assays also reveal that a higher antibody titer is required to immobilize O139 compared to O1, a phenotype that is O139 capsule dependent.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Bishop
authors.forename: Stefan
authors.initials: S
authors.lastname: Schild
authors.forename: Bharathi
authors.initials: B
authors.lastname: Patimalla
authors.forename: Brian
authors.initials: B
authors.lastname: Klein
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial; D002462:Cell Membrane / Q000276:immunology; D002771:Cholera / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007112:Immunity, Maternally-Acquired; D007136:Immunoglobulins / Q000276:immunology*; D051379:Mice; D008892:Milk / Q000276:immunology; D022142:Secretory Vesicles / Q000276:immunology*; D014734:Vibrio cholerae / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022121:Cholera Vaccines; D007136:Immunoglobulins; C042866:antilipopolysaccharide antibodies