Syrian Golden hamsters were vaccinated with the recombinant fusion proteins Ay-ASP-2 and Ay-MTP-1 from the infective larvae of the hookworm Ancylostoma ceylanicum. Vaccines comprised each antigen alone or the combination of the two proteins. All vaccinated group developed high antibody titers (>1:40,000); coadministration of a second antigen did not significantly affect the magnitude of the antibody response. Following challenge, hamsters vaccinated with each single antigen exhibited reductions in worm burden (32% and 28% to Ay-ASP-2 and Ay-MTP-1, respectively) and fecal egg counts (56% and 43%, respectively). A vaccine cocktail, containing both antigens further reduced worm burden (36%) and fecal egg counts (59%) (p<0.001). Moreover, vaccination with the antigen cocktail significantly improved hemoglobin values (p=0.01) and body weights (p=0.001) compared to what achieved with either each antigen or adjuvant alone. Taken together, these data suggest that combination of two or more antigens may present an effective vaccine development strategy to improve protection and/or disease symptoms in affected individuals.