MyD88 signal is required for more efficient induction of Ag-specific adaptive immune responses and antitumor resistance in a human papillomavirus E7 DNA vaccine model

The function of MyD88 signals for induction of adaptive immunity is still controversial. Here we investigate using a human papillomavirus (HPV) 16 E7 DNA vaccine on MyD88 knock out mouse model whether MyD88 signals are required for induction of Ag-specific antibody and cellular responses, as well as antitumor resistance. When injected intramuscularly with E7 DNA vaccines, MyD88 deficient mice displayed antitumor protective responses to tumor cell challenges while having far lower responses than wild type mice. A similar finding was observed in antitumor therapeutic models by intramuscular-electroporation of E7 DNA vaccines. E7 DNA vaccines induced Ag-specific humoral and CD8+ CTL responses in MyD88 deficient mice. However, the levels were much less than those of wild type mice. These data suggest that the immune stimulatory sequence of E7 DNA vaccines and its signaling through MyD88 are not absolutely essential for induction of adaptive immune responses. However, MyD88 deficient mice co-delivered with MyD88 cDNA plus E7 DNA vaccines showed a recovery of Ag-specific IgG and CTL responses, and antitumor immunity to the levels of wild type mice, highlighting the importance of MyD88 signals for augmenting an adaptive immune response. Thus, these data clearly show that MyD88 signals are required only for more efficient induction of Ag-specific humoral and antitumor CD8+ CTL responses in this model.