title: Generation of adult-like antibody avidity profiles after early-life immunization with protein vaccines.
abstract: The capacity to induce high-avidity antibodies following early-life immunization has long been questioned, and the possibility of inducing such antibodies soon after birth is a recognized goal for a number of vaccination strategies. Therefore, we assessed the capacity to develop high-avidity antibodies to peptidic vaccines in 1-week-old BALB/c mice. The dynamics of the generation of antibody molecules of increasing avidity were analyzed on circulating serum antibodies and, where feasible, at the single-cell level on spleen and bone marrow antibody-secreting cells. Two alum-adsorbed protein-based human vaccines, tetanus toxoid (TT) and pertussis toxin, induced neonatal antibody responses with adult-like avidity profiles. This was confirmed at the level of spleen and bone marrow ASC. In contrast, immunization with TT-P30, a 21-mer synthetic peptide containing a TT-immunodominant epitope, trinitrophenyl hapten (TNP) conjugated to ovalbumin or TNP conjugated to Ficoll, induced a much lower avidity profile in early life than in adults. These observations indicate that in murine models the avidity maturation of T cell-dependent antibody responses induced by structurally complex protein vaccines can be fully elicited after early life immunization, as opposed to the maturation of responses induced with short peptides or hapten-based vaccines.
authors.affiliation: World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, Department of Pathology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schallert
authors.forename: Maria
authors.initials: M
authors.lastname: Pihlgren
authors.forename: Jiri
authors.initials: J
authors.lastname: Kovarik
authors.forename: Caroline
authors.initials: C
authors.lastname: Roduit
authors.forename: Chantal
authors.initials: C
authors.lastname: Tougne
authors.forename: Paola
authors.initials: P
authors.lastname: Bozzotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000833:Animals, Suckling / Q000276:immunology; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D000915:Antibody Affinity; D001886:Bordetella pertussis / Q000276:immunology; D003017:Clostridium tetani / Q000276:immunology; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D007107:Immune System / Q000254:growth & development*; D007114:Immunization; D007115:Immunization Schedule; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D014121:Toxoids / Q000008:administration & dosage / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; C020529:TNP-ficoll; D013745:Tetanus Toxoid; D014121:Toxoids; D014301:Trinitrobenzenes; D022223:Vaccines, Subunit; C051093:pertussis toxoid; C038600:trinitrophenyl-ovalbumin; D005362:Ficoll; D010047:Ovalbumin