Vibriobactin antibodies: a vaccine strategy.
A new target strategy in the development of bacterial vaccines, the induction of antibodies to microbial outer membrane ferrisiderophore complexes, is explored. A vibriobactin (VIB) analogue, with a thiol tether, 1-(2,3-dihydroxybenzoyl)-5,9-bis[[(4S,5R)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-5-methyl-4-oxazolyl]carbonyl]-14-(3-mercaptopropanoyl)-1,5,9,14-tetraazatetradecane, was synthesized and linked to ovalbumin (OVA) and bovine serum albumin (BSA). The antigenicity of the VIB microbial iron chelator conjugates and their iron complexes was evaluated. When mice were immunized with the resulting OVA-VIB conjugate, a selective and unequivocal antigenic response to the VIB hapten was observed; IgG monoclonal antibodies specific to the vibriobactin fragment of the BSA and OVA conjugates were isolated. The results are consistent with the idea that the isolated adducts of siderophores covalently linked to their bacterial outer membrane receptors represent a credible target for vaccine development.
Bergeron
Raymond J
RJ
Department of Medicinal Chemistry, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, Florida 32610-0485, USA. rayb@ufl.edu
Bharti
Neelam
N
Singh
Shailendra
S
McManis
James S
JS
Wiegand
Jan
J
Green
Linda G
LG
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology*; D001665:Binding Sites; D002396:Catechols / Q000737:chemistry / Q000276:immunology*; D002417:Cattle; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010080:Oxazoles / Q000737:chemistry / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology; D017262:Siderophores / Q000737:chemistry / Q000276:immunology*; D014734:Vibrio cholerae / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D002396:Catechols; D010080:Oxazoles; D017262:Siderophores; D012710:Serum Albumin, Bovine; C040227:vibriobactin; D010047:Ovalbumin