title: Combined conjugate vaccines: enhanced immunogenicity with the N19 polyepitope as a carrier protein.
abstract: The N19 polyepitope, consisting of a sequential string of universal human CD4(+)-T-cell epitopes, was tested as a carrier protein in a formulation of combined glycoconjugate vaccines containing the capsular polysaccharides (PSs) of Neisseria meningitidis serogroups A, C, W-135, and Y. Good antibody responses to all four polysaccharides were induced by one single immunization of mice with N19-based conjugates. Two immunizations with N19 conjugates elicited anti-MenACWY antibody titers comparable to those induced after three doses of glycoconjugates containing CRM197 as carrier protein. Compared to cross-reacting material (CRM)-based constructs, lower amounts of N19-MenACWY conjugates still induced high bactericidal titers to all four PSs. Moreover, N19-MenACWY-conjugated constructs induced faster and higher antibody avidity maturation against meningococcal C PS than CRM-based conjugates. Very importantly, N19-specific antibodies did not cross-react with the parent protein from which N19 epitopes were derived, e.g., tetanus toxoid and influenza virus hemagglutinin. Finally, T helper epitopes of the N19 carrier protein were effectively generated both in vivo (after immunization with the N19 itself) and in vitro (after restimulation of epitope-specific spleen cells). Taken together, these data show that the N19 polyepitope represents a strong and valid option for the generation of improved or new combined glycoconjugate vaccines.
authors.affiliation: Research Center, Chiron Vaccines, via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Karin
authors.initials: K
authors.lastname: Baraldo
authors.forename: Elena
authors.initials: E
authors.lastname: Mori
authors.forename: Antonella
authors.initials: A
authors.lastname: Bartoloni
authors.forename: Francesco
authors.initials: F
authors.lastname: Norelli
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Oretta
authors.initials: O
authors.lastname: Finco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000915:Antibody Affinity; D001424:Bacterial Infections / Q000276:immunology / Q000517:prevention & control; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000008:administration & dosage / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D006001:Glycoconjugates / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D006001:Glycoconjugates; D007074:Immunoglobulin G; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin)