Correlations among measles virus-specific antibody, lymphoproliferation and Th1/Th2 cytokine responses following measles–mumps–rubella-II (MMR-II) vaccination

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Abstract
Immunity to measles is conferred by the interplay of humoral and cellular immune responses, the latter being critical in maintaining long‐term recall response. Therefore, it is important to evaluate measles‐specific humoral and cellular immunity in populations several years after vaccination and understand the correlations among these measures of immunity. We examined measles‐specific antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon (IFN)‐γ and interleukin (IL)‐4, in a population‐based cohort of healthy children from Olmsted County, Minnesota after two doses of measles–mumps–rubella‐II (MMR‐II) vaccine. We detected positive measures of measles‐specific cellular and humoral immunity in the majority of our study population. However, a small proportion of subjects demonstrated an immune response skewed towards the Th2 type, characterized by the presence of either IL‐4 and/or measles‐specific antibodies and a lack of IFN‐γ production. Further, we observed a significant positive correlation between lymphoproliferation and secretion of IFN‐γ (r = 0·20, P = 0·0002) and IL‐4 (r = 0·15, P = 0·005). Measles antibody levels were correlated with lymphoproliferation (r = 0·12, P = 0·03), but lacked correlation to either cytokine type. In conclusion, we demonstrated the presence of both long‐term cellular and humoral responses after MMR‐II vaccination in a significant proportion of study subjects. Further, a positive correlation between lymphoproliferation and IL‐4 and IFN‐γ suggests that immunity to measles may be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased response observed in a subset of our subjects may be insufficient to provide long‐term immunity against measles. Further examination of the determinants of Th1 versus Th2 skewing of the immune response and long‐term follow‐up is needed.