A step ahead - Infant protection through maternal immunization

The prevention of severe infectious diseases in children through immunization is a well-recognized, beneficial, and cost-effective strategy worldwide.(17) Neonates and young infants continue to be vulnerable to significant morbidity and mortality caused by bacterial and viral pathogens. With the exception of hepatitis B virus (HBV) vaccine, active immunization has not been successful in neonates because of the immaturity of their immune responses and the fact that protective immunity requires several weeks to develop. The safety of different vaccines in the younger age groups remains a concern and requires careful evaluation. The observation that maternal antibodies transmitted transplacentally before birth confer protection against some viral and bacterial diseases during the first months of life is important for designing disease-prevention strategies in this population.(30, 35, 54, 75, 76, 78, 81) The development of newer vaccines against bacterial and viral pathogens provides unique opportunities and increasing possibilities to protect neonates and young infants against life-threatening diseases.(26, 64) The goal of maternal immunization is to permit young infants to acquire sufficient levels of pathogen-specific antibodies to resist infections during a period of increased susceptibility. Enhancing immunity in mothers has already proven to be a safe and effective strategy that also provides protection for pregnant women.(36) Women in the later stages of pregnancy are capable of producing adequate amounts of antibodies in response to vaccines. IgG antibodies, especially of the IgG1 subtype, readily cross the placenta, particularly in the last 4 to 6 weeks of gestation.(29) Term newborns receive similar or higher levels of antibody than those in their mothers because of active transplacental transport.(23,24,57) Neonatal IgG levels correlate with gestational age, and the duration of protection correlates with the serum levels of antibodies present at birth. Infants born with high antibody concentrations could be protected for the duration of the time required for their immune systems to respond to active immunization. An additional benefit might be the passage of antibodies (IgA) in breast milk for a longer period of time in breast-fed infants. Premature infants are unlikely to benefit from maternal immunization because of decreased antibody transfer before delivery.(22) The most prevailing concern with the use of vaccines during pregnancy is the safety of fetuses and newborns. Although vaccines used in pregnant women in the past have not been associated with a higher risk for infant or maternal adverse outcomes, candidate vaccines for maternal immunization are subject to rigorous testing and screening by vaccine manufacturers, clinicians, and governmental agencies.(6) Because vaccines for maternal immunization should be used during the later stages of pregnancy, when fetuses are fully developed, potential risks are likely to be limited to events that would compromise the course of the normal gestation, such as induction of premature labor or the development of severe vaccine reactions in mothers. The theoretic risk in infants for tolerance to the vaccine agents is minimized by maternal immunization in the last trimester of pregnancy. Priming of an infant's immune system by passively acquired antibodies and the inhibition of subsequent responses to natural infection or immunization, however, has not been consistently documented in carefully conducted studies.(26, 64) This has not been shown to occur when immunoglobulin or monoclonal antibody products are exogenously administered to infants.(90, 91)