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.

Unresponsiveness to lymphoid-mediated signals at the neonatal follicular dendritic cell precursor level contributes to delayed germinal center induction and limitations of neonatal antibody responses to T-dependent antigens.

The factors limiting neonatal and infant IgG Ab responses to T-dependent Ags are only partly known. In this study, we assess how these B cell responses are influenced by the postnatal development of the spleen and lymph node microarchitecture. When BALB/c mice were immunized with alum-adsorbed tetanus toxoid at various stages of their immune development, a major functional maturation step for induction of serum IgG, Ab-secreting cells, and germinal center (GC) responses was identified between the second and the third week of life.

Immunogenicity and protective efficacy of neonatal vaccination against Bordetella pertussis in a murine model: evidence for early control of pertussis.

A significant resurgence of early cases of pertussis is being observed in infants too young to have yet completed their three-dose vaccination schedule. In this study, murine models of immunization and Bordetella pertussis challenge were adapted to early life. This allowed comparative evaluation of immunogenicity and protective efficacy of immunization initiated in the neonatal period (7-day-old mice) or in infancy (3-week-old mice) with diphtheria-tetanus-whole-cell pertussis (DTPw) and diphtheria-tetanus-acellular pertussis (DTPa) vaccines.

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.

Induction of adult-like antibody, Th1, and CTL responses to measles hemagglutinin by early life murine immunization with an attenuated vaccinia-derived NYVAC(K1L) viral vector.

Although initially developed in adult animals, novel viral vectors expressing recombinant measles antigens must eventually prove their success in the early life setting, where the efficacy of the currently used live-attenuated measles virus vaccine is limited. The immunological requirements for vaccine candidates include the generation of protective antibody responses as well as the induction of Th1 and cytotoxic T lymphocytes (CTL) responses, which is challenging in the neonatal setting. Here, we report that young BALB/c mice immunized with a single dose of a vaccinia-based NYVAC(K1L) vector generate adult-like antihemagglutinin (HA) antibody responses as well as adult-like Th1 and CTL responses.