COMPLEXITY OF THE CYTOKINE AND ANTIBODY-RESPONSE ELICITED BY IMMUNIZING MICE WITH PLASMODIUM-YOELII CIRCUMSPOROZOITE PROTEIN PLASMID DNA

The number, type, and location of cytokine- and Ab-secreting cells act ivated in mice immunized and boosted with plasmid DNA encoding the cir cumsporozoite protein of the malarial parasite Plasmodium yoelii (PyCS P) were monitored. The initial humoral response was localized to the d raining lymph nodes and was characterized by the production of IgG1 an ti-PyCSP Abs and the Th2 cytokine IL-4. In contrast, the secondary res ponse was dominated by lFN-gamma production (a Th1 cytokine) and the s ecretion of IgG2a anti-PyCSP Abs in the spleen. PyCSP DNA and mRNA wer e detected only in the quadriceps muscles (sites of plasmid injection) , yet these sites lacked either cytokine- or Ab-secreting cells. These findings indicate that circulating lymphocytes encounter plasmid-enco ded Ag in the muscle bed, initiate a humoral response in the draining lymph nodes, and then seed distal lymphoid organs. Profound difference s were observed between the primary and secondary immune responses ind uced by plasmid immunization, which may influence vaccine efficacy.