Generation of adult-like antibody avidity profiles after early-life immunization with protein vaccines

Eur J Immunol. 2002 Mar;32(3):752-60. doi: 10.1002/1521-4141(200203)32:3<752::AID-IMMU752>3.0.CO;2-5.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Animals, Suckling / immunology
  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / immunology*
  • Antibody Affinity*
  • Bordetella pertussis / immunology
  • Clostridium tetani / immunology
  • Ficoll / analogs & derivatives*
  • Ficoll / immunology
  • Immune System / growth & development*
  • Immunization Schedule
  • Immunization*
  • Immunodominant Epitopes / immunology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • Specific Pathogen-Free Organisms
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology
  • Toxoids / administration & dosage
  • Toxoids / immunology
  • Trinitrobenzenes / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology*

Substances

  • Antibodies, Bacterial
  • Immunodominant Epitopes
  • Immunoglobulin G
  • Peptide Fragments
  • TNP-ficoll
  • Tetanus Toxoid
  • Toxoids
  • Trinitrobenzenes
  • Vaccines, Subunit
  • pertussis toxoid
  • trinitrophenyl-ovalbumin
  • Ficoll
  • Ovalbumin