Safety and efficacy of neonatal vaccination in animal models
Multiple studies have documented that certain vaccines are apparently safe and effective when administered in utero or to newborn animals. Although serious side-effects due to vaccination of neonatal animals are generally rare, passive surveillance in the U.K. of dog vaccinations has demonstrated a relatively high prevalence of vaccine-associated adverse effects in very young animals [68]. The most common adverse event appears to be facial edema and pruritis, believed due to immediate (type I) hypersensitivity reaction triggered by degranulation of mast cells sensitized by maternal IgE. These potential adverse effects may be secondary to high bovine serum albumin content in canine vaccines and are most prevalent in small breed dogs, suggesting that dose reduction may be in order. Alum- or lipid-adjuvanted vaccines induce greater tissue inflammation than non-adjuvanted vaccines after subcutaneous administration in 14–16 week old kittens [69].
Examples of efficacy of neonatal vaccination in animal models include avian studies of the live herpes virus of turkeys (HVT) vaccine, aimed at preventing the α-herpesvirus neoplastic Marek's disease of chickens, demonstrate protection even when administered in ovo or at day 1 [70]. Beagle puppies have been vaccinated sub-cutaneously with modified live canine parvovirus at 1 day of age [63]. Both kinetics and magnitude of Ab response were similar to those of older puppies. In this model, vaccination after colostral ingestion or of puppies of convalescent dams with high anti-canine parvovirus titers was unsuccessful, illustrating the potential inhibitory role of maternal antibody. However, under certain circumstances the hurdle of maternal Ab can be overcome. Puppies born to dams boosted during pregnancy with killed adjuvanted rabies vaccine and whom received colostral immunity, nevertheless mounted protective Ab responses after immunization with RABISIN vaccine comprised of rabies virus glycoproteins and aluminum hydroxide adjuvant [63]. The authors speculate that either greater antigenic content and/or vector properties may allow more efficient Ag presentation. Thus under certain conditions murine and human neonates can mount effective adaptive immune responses. Although these studies do not define the mechanisms by which the vaccine studied overcame impairments in neonatal immunity, they do illustrate the possibility of effective vaccination at birth.