Of note, in assessing the potential efficacy of neonatal vaccines, although the prevention of infection is the ultimate goal and most important end-point, correlates of vaccine-induced immunity must be carefully considered, as recently reviewed by Plotkin [23]. Both quantitative and qualitative (i.e., functional activity) of Ab can serve as “co-correlates” and surrogate markers for protection and are predominantly used in vaccine studies. Nevertheless, cell-mediated immunity is critical in protection against intracellular infections and, through the function of CD4+ cells, necessary to enhance B cell development, as illustrated below in the case of BCG.
Early studies with whole cell pertussis vaccine given alone or combined with diphtheria and tetanus vaccines within the first 24 hours of life demonstrated safety, without any signs of erythema, infiltration, fever, irritability, vomiting or anorexia [24]. However, pertussis immunization at birth resulted in serologically inadequate responses and blunting of booster responses to pertussis in 75% of study subjects until 5 months of age, suggestive of antigen-specific “immunologic paralysis” or tolerance induced by the immunization. This failure was believed to be independent of any effects of MatAb, as these were low or undetectable. In contrast, immunization at 3 weeks of age resulted in adequate serologic response [24].
Purified polysaccharide vaccine (PRP), the first vaccine licensed to prevent Hib disease, was neither immunogenic in neonates nor consistently immunogenic in children older than 18 months [25]. In contrast, the current Hib conjugate vaccine, diphtheria CRM 197 protein conjugate (HbOC) is given as a series of three injections starting at two months of age. Lieberman et al. [25] attempted to enhance antibody response to HbOC by administering the diphtheria-tetanus (DT) vaccine at birth, only to find that at 7 months, children exposed to DT at birth had a lower antibody response than those immunized beginning at 2 months of age. Impairment in neonatal Th1 helper T cell response compared to adults may contribute to reduced neonatal responses to some vaccines. For example, after oral polio vaccination (OPV), young infants produce a relatively weak IFN-γ and cell-mediated response compared to adults, although they produce high titers of neutralizing antibodies [26], thought to be essential for protective immunity against poliovirus [27].