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Generation of adult-like antibody avidity profiles after
early-life immunization with protein vaccines.
Schallert N, Pihlgren M, Kovarik J, Roduit C, Tougne C, Bozzotti P, Giudice
G, Siegrist CA, Lambert PH.
World Health Organization Collaborating Center for Vaccinology and Neonatal
Immunology, Departments of Pathology and Pediatrics, University of Geneva
Medical School, Geneva, Switzerland.
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 goalfor 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-adsorbedprotein-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.
PMID: 11870619 [PubMed - as supplied by publisher]
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