The hepatitis A vaccines are highly immunogenic and without serious adverse effects. Therefore, the interaction between the antigen and the immune system must be very efficient. This study proposes to examine the cytokine response as an immune mechanism driving the antibody response to hepatitis A immunization and model the pharmacodynamics of this response. Our primary hypothesis is that the interleukin-4 (IL-4) production stimulated by hepatitis A immunization will predict the height of the antibody levels to hepatitis A immunization. To substantiate this hypothesis, we will immunize 25 hepatitis A seronegative subjects who will be followed for two weeks with serial blood draws to determine IL-4 production using three different strategies. Peripheral blood mononuclear cells (PBMC) will be cultured and spontaneous IL-4 production will be measured by ELISA in the supernatant of the cell cultures. IL-4 gene expression will be measured by extracting mRNA from PBMC. The mRNA will be probed with an IL-4 specific DNA probe and the amount of hybridized mRNA will be measured by capillary electrophoresis. Finally, we will measure IL-4 levels in the serum obtained from subjects.
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