Immune responsiveness in the neonatal period

Abstract

The maintenance of pregnancy requires suppression of the maternal immune system which would naturally recognize the developing fetus as an allograft and seek to destroy it by mounting a Th1 regulated cytotoxic immune response. During pregnancy a range of soluble factors are produced by the placenta which switch maternal immune regulation towards a protective Th2 phenotype. These factors also influence the developing fetal immune system and all newborns initially have an immunological milieu skewed towards Th2 immunity. Vaccination during the neonatal period must therefore overcome the dual challenge of the inhibitory effect of maternally derived antibody and this natural Th2 regulatory environment. One means of overcoming these obstacles is by the use of adjuvant systems that can redirect the neonatal immune response towards an appropriate Th1 regulated reaction that affords protection from infectious disease. In this overview, experiments are described in which viral antigens incorporated into immune stimulatory complexes (ISCOMs) are able to induce immune responses with balanced Th1 and Th2 regulation in neonatal mice, as evidenced by the nature of the IgG subclass response and cytokine profile, and the induction of cytotoxic lymphocytes. ISCOM adjuvanted vaccines are able to induce similar protective immunity in the newborn of larger animal species including cattle, horses and dogs.