One of the major goals of the USPHS is the regional elimination of measles by the year 2000, a goal that is achievable due to an increase in immunization rates and implementation of a two dose schedule for measles vaccine. However, there are still some unanswered questions regarding optimal use of measles vaccines . For example, research is needed in order to understand the safest method for immunization of immunocompomised children, such as those with HIV infection, who could suffer serious disease as the result of measles infection or serve as a focus of persistent shedding and spread of measles virus that could impede eradication efforts. In addition, increasing numbers of infants are born to mothers with vaccine induced immunity. These mothers have lower levels of measles antibody than mothers with immunity induced by wild type measles infection. As a result, infants born to vaccinated mothers have lower levels of passively acquired antibody at birth and these infants become susceptible to measles infection early, with loss of antibody by 6-9 months of age. Previously, vaccine failure in infants less than 12 months of age was thought to result from neutralization of vaccine virus with passively acquired antibody. It is not known if immunization of young infants with or without passive antibody would prime for measles specific cell mediated immune responses, or if immaturity of the infant immune system contributes to vaccine failure. Dr. Hayley Gans, along with Drs. Maldonado, DeHovitz and Arvin at Stanford Unversity Medical Center, evaluated IL-12, IFN-gamma and T-cell lymphoproliferative responses in infants immunized with measles vaccine at 6, 9 and 12 months of age. Our laboratory provided support, and determined levels of measles antibody in 162 infants prior to and following immunization with measles vaccine. T cell lymphoproliferative responses were induced in 71, 69 and 62% of infants immunized at 6, 9 or 12 months, respectively, and occurred in the presence or absence of passive antibody. Likewise, passively acquired measles antibody had no effect on the ability of measles to induce IL-12 or IFN-gamma from PBMCs of immunized infants. Interestingly, there were no differences between T- cell or cytokine responses among infants at 6, 9 or 12 months of age, however, responses of infants were diminished when compared to the responses of immunized adults, suggesting that the lower responses were age related. In order to investigate this further, infant PBMCs were stimulated with measles antigen in the presence and absence of recombinant IL12. Infant cells stimulated with virus and rIL12 produced higher levels of IFNgamma (747 pg/ml)than when stimulated with measles antigen alone, however,the levels of IFNgamma produced were significantly less than levels produced from adult PBMCs,(1634 pg/ml),stimulated under similar conditions. These results suggest that the immune response to measles vaccine in early life may be characterized by T cell priming and diminished TH1 type cytokine responses may be age related.
