Vaccination of neonates: problem and issues.

Many serious infectious diseases occur early in life; efficacious vaccination of neonates has been a longstanding goal in both human and veterinary medicine. Efforts to immunize in the first weeks of life, in various species, have had limited success in general. This has been attributed to a combination of immaturity of the neonatal immune system and interference by maternal antibodies. Most studies of neonatal immune responsiveness have been carried out in neonatal mice, or by examination of cellular components of human umbilical cord blood. Both approaches have their limitations. The current review describes factors, including corticosteroids, complement proteins, cytokines, maternal lymphocytes and antibodies, which may influence immune responses of neonates, comparing data from studies of domestic animals and humans. Neonates are highly dependent on passive (maternal) antibodies for protection against a wide range of pathogens. These maternal antibodies have been noted to interfere with active immune responses to many, but not all, vaccines. Various theories have been proposed to explain this phenomenon, including epitope masking, clearance of immune complexes and FcγRII mediated regulation of B cells. Remarkably, many studies examining the effects of passive antibodies on immune responses of adults, have demonstrated immune enhancing effects. The evidence for enhancing and suppressive effects of passive antibodies on antigen uptake, processing and regulation of lymphocyte responses is reviewed. Since maternal antibodies (as present in neonates) differ in subisotypes and affinity from the passive antibodies often used in experimental systems, here is a need for better experimental models investigating the effects of bona fide maternal antibodies on immune responses of neonates (not adult surrogates). Vaccines can be optimized for use in neonates - by making better use of existing vaccine technologies and by harnessing the potential of recent immunological and technological advances.