CpG-motifs enhance initial and sustained primary tetanus-specific antibody secreting cell responses in spleen and bone marrow, but are more effective in adult than in neonatal mice.

Unmethylated CpG oligonucleotides (CpG-ODN) increase adult and neonatal primary antibody responses to T-dependent antigens, at yet unidentified stages of antigen-specific B cell differentiation. In adult mice, a single dose of CpG-ODN adjuvanted tetanus toxoid (TT) vaccine markedly enhanced and prolonged splenic TT-specific antibody-secreting-cell (ASC) responses and significantly increased the size of the bone marrow (BM) ASC pool. Surprisingly, this was not associated with changes of germinal center (GC) numbers, size, apoptosis or function. In 1-week-old mice, CpG-ODN also enhanced TT-specific splenic ASC responses, but failed to correct limitations of the GC reaction and of the development of the BM ASC pool.

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

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.