Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice.
We have previously demonstrated the full-length gonococcal transferrin binding proteins (TbpA and TbpB) to be promising antigens in the development of a protective vaccine against Neisseria gonorrhoeae. In the current study we employed a genetic chimera approach fusing domains from TbpA and TbpB to the A2 domain of cholera toxin, which naturally binds in a non-covalent fashion to the B subunit of cholera toxin during assembly. For one construct, the N-terminal half of TbpB (NB) was fused to the A2 subunit of cholera toxin. In a second construct, the loop 2 region (L2) of TbpA was genetically fused between the NB domain and the A2 domain, generating a double chimera. Both chimeras were immunogenic and induced serum bactericidal and vaginal growth-inhibiting antibodies. This study highlights the potential of using protective epitopes instead of full-length proteins in the development of an efficacious gonococcal vaccine.
Price
Gregory A
GA
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298, USA.
Masri
Heather P
HP
Hollander
Aimee M
AM
Russell
Michael W
MW
Cornelissen
Cynthia Nau
CN
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D002772:Cholera Toxin / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005260:Female; D006069:Gonorrhea / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D050296:Microbial Viability / Q000276:immunology*; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000254:growth & development* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA; D033881:Transferrin-Binding Protein A / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D033882:Transferrin-Binding Protein B / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014621:Vagina / Q000382:microbiology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D011993:Recombinant Fusion Proteins; D033881:Transferrin-Binding Protein A; D033882:Transferrin-Binding Protein B; D002772:Cholera Toxin