title: Exploiting chimeric human antibodies to characterize a protective epitope of Neisseria adhesin A, one of the Bexsero vaccine components.
abstract: Neisseria adhesin A (NadA) is one of the antigens of Bexsero, the recently licensed multicomponent vaccine against serogroup B Neisseria meningitidis (MenB). NadA belongs to the class of oligomeric coiled-coil adhesins and is able to mediate adhesion and invasion of human epithelial cells. As a vaccine antigen, NadA has been shown to induce high levels of bactericidal antibodies; however, the domains important for protective response are still unknown. In order to further investigate its immunogenic properties, we have characterized the murine IgG1 mAb (6E3) that was able to recognize the 2 main antigenic variants of NadA on the surface of MenB strains. The epitope targeted by mAb 6E3 was mapped by hydrogen-deuterium exchange mass spectrometry and shown to be located on the coiled-coil stalk region of NadA (aa 206-249). Although no serum bactericidal activity was observed for murine IgG1 mAb 6E3, functional activity was restored when using chimeric antibodies in which the variable regions of the murine mAb 6E3 were fused to human IgG3 constant regions, thus confirming the protective nature of the mAb 6E3 epitope. The use of chimeric antibody molecules will enable future investigations of complement-mediated antibody functionality independently of the Fc-mediated differences in complement activation.
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Isabella
authors: I
authors: Bertoldi
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Agnese
authors: A
authors: Faleri
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Barbara
authors: B
authors: Galli
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Paola
authors: P
authors: Lo Surdo
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Alessia
authors: A
authors: Liguori
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Nathalie
authors: N
authors: Norais
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Laura
authors: L
authors: Santini
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Vega
authors: V
authors: Masignani
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy.
authors: Mariagrazia
authors: M
authors: Pizza
authors: Novartis Vaccines and Diagnostics, GlaxoSmithKline, Siena, Italy marzia.m.giuliani@gsk.com.
authors: Marzia Monica
authors: MM
authors: Giuliani
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D041961:Deuterium Exchange Measurement / Q000379:methods; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D008589:Meningococcal Infections / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D009343:Neisseria / Q000276:immunology*
chemical_list: C570015:4CMenB vaccine; D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000939:Epitopes; D022401:Meningococcal Vaccines
keywords: MenB vaccine; bactericidal epitope; epitope mapping; hydrogen-deuterium exchange; meningococcal antigen