title: Investigating the immunodominance of carbohydrate antigens in a bivalent unimolecular glycoconjugate vaccine against serogroup A and C meningococcal disease.
abstract: Multicomponent constructs, obtained by coupling different glycans to the carrier protein, have been proposed as a way to co-deliver multiple surface carbohydrates targeting different strains of one pathogen and reduce the number of biomolecules in the formulation of multivalent vaccines. To assess the feasibility of this approach for anti-microbial vaccines and investigate the potential immunodominance of one carbohydrate antigen over the others in these constructs, we designed a bivalent unimolecular vaccine against serogroup A (MenA) and C (MenC) meningococci, with the two different oligomers conjugated to same molecule of carrier protein (CRM197). The immune response elicited in mice by the bivalent MenAC construct was compared with the ones induced by the monovalent MenA and MenC vaccines and their combinations. After the second dose, the bivalent construct induced good levels of anti-MenA and anti-MenC antibodies with respect to the controls. However, the murine sera from the MenAC construct exhibited good anti-MenC bactericidal activity, and very low anti-MenA functionality when compared to the monovalent controls. This result was explained with the diverse relative avidities against MenA and MenC polysaccharides, which were measured in the generated sera. The immunodominant effect of the MenC antigen was fully overcome following the third immunization, when sera endowed with higher avidity and excellent bactericidal activity against both MenA and MenC expressing strains were elicited. Construction of multicomponent glycoconjugate vaccines against microbial pathogens is a feasible approach, but particular attention should be devoted to study and overcome possible occurrence of immune interference among the carbohydrates.
authors.affiliation: Novartis Vaccines and Diagnostics, Research Center, Via Fiorentina 1, 53100, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Adamo
authors.forename: Alberto
authors.initials: A
authors.lastname: Nilo
authors.forename: Carole
authors.initials: C
authors.lastname: Harfouche
authors.forename: Barbara
authors.initials: B
authors.lastname: Brogioni
authors.forename: Simone
authors.initials: S
authors.lastname: Pecetta
authors.forename: Giulia
authors.initials: G
authors.lastname: Brogioni
authors.forename: Evita
authors.initials: E
authors.lastname: Balducci
authors.forename: Vittoria
authors.initials: V
authors.lastname: Pinto
authors.forename: Sara
authors.initials: S
authors.lastname: Filippini
authors.forename: Elena
authors.initials: E
authors.lastname: Mori
authors.forename: Marta
authors.initials: M
authors.lastname: Tontini
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Romano
authors.forename: Paolo
authors.initials: P
authors.lastname: Costantino
authors.forename: Francesco
authors.initials: F
authors.lastname: Berti
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D002240:Carbohydrate Sequence; D006001:Glycoconjugates / Q000737:chemistry / Q000276:immunology*; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D007279:Injections, Subcutaneous; D008585:Meningitis, Meningococcal / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000737:chemistry / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology*; D065288:Serogroup; D018074:Vaccines, Conjugate; D022223:Vaccines, Subunit
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D006001:Glycoconjugates; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; D022223:Vaccines, Subunit