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Objective. To identify the most effective dose of filarial rBmALT-2 and rWbGST alone or in combination against B. malayi infection in vitro and in vivo. Methods. Mastomys (n = 5–7/group) received intramuscular (i.m.) injection with three different doses (25, 50, and 100 μg) of rBmALT-2 or rWbGST, either alone or in combination with alum as the adjuvant. Protective immunity was studied by in vivo and in vitro cytotoxicity assay. To evaluate the cellular immune response, splenocyte proliferation and cytokine profile were assessed. Results. Serological results revealed a substantial (p<0.005) induction of IgG1, IgG2a, and IgG3 responses in vaccinated Mastomys. Mastomys immunized with 50 μg rBmALT-2 + alum induced 79–81% killing against the L3 larvae challenge in vivo and in vitro ADCC assay (p<0.005); whereas rWbGST + alum alone or in combination with rBmALT-2 + alum induced 63–68% killing (p<0.005) in vivo and in vitro. Antigen-specific cytokine profiles of Mastomys vaccinated with either BmALT-2, WbGST or a combination showed elevated IL-10, IL-4, and IFN-γ levels, signifying both Th1 and Th2 immune response. Conclusions. These findings suggest that immunization of Mastomys with a 50 μg/dose of rBmALT-2 + alum four times at a 4-week interval demonstrated considerable protection against B. malayi infection.