title: Sortase-conjugation generates a capsule vaccine that protects guinea pigs against Bacillus anthracis.
abstract: Capsules protect bacteria against phagocytic clearance. Capsular polysaccharides or polyglutamates have evolved also to resist antigen presentation by immune cells, thereby interfering with the production of opsonophagocytic antibodies. Linking capsular material to a carrier protein stimulates its presentation to the immune system. For many conjugate vaccines this is achieved by a process of random chemical cross-linking. Here we describe a new technology, designated sortase-conjugation, which generates a single amide bond between the C-terminal end of a carrier protein and the capsular material. Sortase-conjugation was used to link the poly-D-γ-glutamic acid (PDGA) capsule of Bacillus anthracis to the receptor binding domain (D4) of protective antigen (PagA). When used as a vaccine, PDGA-D4 conjugate elicited robust antibody responses against both capsule and D4. Immunization with PDGA-D4 afforded guinea pigs complete protection against anthrax challenge with wild-type or pagA mutant B. anthracis Ames.
authors.affiliation: Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Garufi
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Wang
authors.forename: So-Young
authors.initials: SY
authors.lastname: Oh
authors.forename: Hannah
authors.initials: H
authors.lastname: Maier
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Missiakas
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology*; D016667:Bacterial Capsules / Q000737:chemistry / Q000276:immunology*; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D051379:Mice; D008810:Mice, Inbred C57BL; D011099:Polyglutamic Acid / Q000737:chemistry / Q000276:immunology*; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002352:Carrier Proteins; D018074:Vaccines, Conjugate; C030325:anthrax toxin; D011099:Polyglutamic Acid