A Schistosoma mansoni adult worm cDNA expression library was screened using rabbit IgG against PIII, an adult worm protein fraction, already known to possess protective and immunomodulating effects to a challenge infection in mice. A positive cDNA clone was selected and characterized. The cDNA screened encodes a protein (P44) with an ORF of 1089 bp and an amino acid sequence of 363 residues with a predictable molecular weight of 44 kDa. The P44 amino acid sequence exhibits 100% identity to the fructose 1,6 bisphosphate aldolase of S. mansoni, 66% to Homo sapiens and 66% to Mus musculus. The cDNA was cloned into a pGEX-4T-3 vector and expressed in Escherichia coli as a fusion protein (GST/P44). Mice vaccinated with recombinant P44 were able to develop high levels of IgG or IgG1 and displayed low levels of IgG2a isotype. Moreover, immunization of mice with this antigen induced a significant protection of 57% against a challenge infection and significant decrease in hepatic granuloma formation. Our results demonstrate that granuloma modulation can be targeted for pathology elimination through vaccination. This represents an advance in schistosome vaccinology and allows for the development of a therapeutic as well as a prophylactic vaccine.