Effects of Antenatal and Postnatal Environments on CD4 T-Cell Responses to Mycobacterium bovis BCG in Healthy Infants in The Gambia

The Mycobacterium bovis BCG vaccine has a poor record of efficacy in low-income tropical settings. Against this background, we evaluated the immune response of infants to mycobacterial antigens over the 2 years following BCG vaccination at birth by measuring the gamma interferon (IFN-), interleukin-2 (IL-2), and CD154 responses of CD4 T cells. Similar numbers of cells expressed IFN- in infants, 4- to 5-year-old children, and adults, while CD154 was not expressed at comparable levels until the second year of infancy. The IL-2 response remained relatively low in infants, children, and adults but correlated negatively with mother’s body mass index and was highest among infants born to Mandinka mothers. Similarly, infants born in the wet season had a stronger CD154 response than those born in the dry season throughout the 2 years of the study. We conclude that the prenatal and perinatal environments have a lasting effect on the response of infants to the BCG vaccine. Mycobacterium tuberculosis is a major cause of infectious disease worldwide, especially in low-income countries. Although about one-third of the world’s population are infected (9), the overwhelming majority do not develop tuberculosis. The mechanisms that underlie the ability or failure to contain M. tuberculosis infection remain obscure. It has been suggested that protective immunity depends on containment of the initial infection (10), although it is not clear whether certain individuals are predisposed to be able to do so or what might prevent them from doing so. Several studies have suggested an influence of the antenatal environment on subsequent ability to mount immune responses and fight disease, as maternal body mass index (BMI) and season of birth influence antibody responses to vaccines (24, 29, 30), thymus development (6, 23), and even mortality during adulthood (27, 28). The effect of season of birth has been most intensively studied in The Gambia, where there is a marked decrease in energy intake as stored food from the previous harvest becomes scarce during the wet season, which is also a period of intense agricultural labor largely carried out by women. Consequently, there is a marked seasonal fluctuation in energy balance during pregnancy that affects the birth weight of offspring (38).