Lymphatic filariasis is a mosquito borne parasitic infection that cause severe economic burden in several parts of the world. Currently there is no vaccine available to prevent this infection in human. Multidrug therapy is effective, however, requires annual treatment and there is significant concern of drug resistance. In this manuscript we describe development of a multivalent DNA based vaccine comprising BmALT-2 and BmHSP antigens of lymphatic filariasis. Challenge experiments using third stage infective larvae of Brugia malayi in a mouse model suggested that nearly 90% protection can be achieved using the multivalent formulation in a DNA prime protein boost approach. The vaccination regimen induced significant IgG antibody responses and ELISPOT analysis for secreted cytokines from the spleen cells of vaccinated animals showed that these cells produce significant amount of IL-4. Results from this study thus show that a multivalent vaccine formulation of BmALT-2 and BmHSP is an excellent vaccine for lymphatic filariasis and significant protection can be achieved against a challenge infection with B. malayi in a mouse model.