Inadequate immunogenicity of most vaccines at birth
Immunization in early life is a major public health imperative, but remains a challenging field. The neonatal immunological milieu, skewed towards Th2 immunity to prevent recognition of the developing fetus as an allograft by the maternal immune system [20], represents an important obstacle that vaccination during neonatal period must overcome. In addition to the challenge posed by immaturity of the neonatal leukocyte compartment, effective neonatal vaccines, must also overcome the potential inhibitory effect of MatAb [20]. It is believed that inhibition of adaptive immune responses by MatAb depends on the ratio between MatAb titers and vaccine antigen dose and is due to determinant-specific masking of B cell epitopes [21]. Infant APC uptake and T cell responses appear to be largely unaffected. For example, with respect to the Haemophilus influenzae type b (Hib)-conjugate vaccines, MatAb to the tetanus toxoid (TT) carrier protein inhibit infant responses to TT, but do not inhibit Ab responses to the Hib polysaccharide moiety [22]. Thus MatAb result in specific masking of TT but not of Hib antigenic determinants to infant B cells, preserving APC uptake of MatAb:Ag immune complexes, and allowing response to the Hib polysaccharide moiety. Overall, responses of human newborns to vaccines are not predictable from studies of older infants or adults. Nevertheless, several vaccines have been shown to elicit a clinically significant immunogenic response at birth, as reviewed below.