Prophylactic efficacy of Sm-p80 was tested in the mouse model using DNA priming and boosting with protein approach. However, the novelty of the approach utilized in this study is that both the DNA priming and protein boosting was performed on a single day and no further vaccine inoculations were given to mice; the animals were challenged 1 month after the initial vaccine administration. Using this approach, significant reduction in worm burden (33 to 57 %) and marked decrease in egg retention in tissues (34 to 66%) was observed. Robust antibody titers and upregulation of cytokines (IL-1α/β, IL-12α, and IFN-γ) appears to correlate with the protection. This approach of administering vaccine on a single day could be greatly helpful in the field setting because it will eliminate the compliance issues that may arise with multiple boosters that may be required for optimal efficacy for some vaccines.