Prior research by our laboratory has demonstrated that stressful events experienced by the pregnant female monkey can affect her fetus and alter the development of several important immune responses in her young infant. The proposed studies will further investigate the relative vulnerability of the fetus by assessing the long-term effects of prenatal disturbance on immune responses and disease susceptibility during the first year of life. This research will also extend previous observations of a differential vulnerability of male and female infants. Immune assessment of the infant rhesus monkeys will focus on the development of lymphocyte cytotoxic responses, circulating levels of various cell subsets, and antibody responses. The potential clinical significance of the physiological alterations induced by prenatal disturbance will be evaluated by determining the infant's antibody responses to Haemophilus influenzae vaccination and, at an older age, by inoculation with Salmonella typhimurium. This attenuated strain of Salmonella is being used to deliver viral antigen to the mucosal immune system -- an approach that is currently being tested in vaccine studies to prevent transmucosal infection with simian immunodeficiency virus. In addition to assessing the immune effects of pregnancy disturbance in a reliable nonhuman primate model, the research will determine whether there are periods of particular vulnerability during pregnancy. One experiment will also assess whether the absence of breast milk and its soluble immune products exacerbates the effects of prenatal disturbance. The goal of the research program is to refine our understanding of how prenatal events influence the development of immune competence and facilitate the establishment of normal set points for certain physiological responses in the young infant.
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