Pneumolysin (Ply) and its variants are protective against pneumococcal infections in animal models and, as a Toll like receptor 4 agonist; pneumolysin has been reported to be a mucosal adjuvant. DnaJ has been approved to be a useful candidate vaccine protein, we therefore designed novel fusion proteins of ΔA146Ply-DnaJ and DnaJ-ΔA146Ply to test whether they are protective against focal and lethal pneumococcal infections and their potential protective mechanisms. The purified proteins were used to intranasally immunize the animals without additional adjuvant. Immunization with DnaJ-ΔA146Ply or DnaJ plus ΔA146Ply could significantly reduce the S. pneumoniae colonization in nasopharynx and lung relative with DnaJ alone. Additionally, we observed the best protection for DnaJ-ΔA146Ply immunized mice after challenge with lethal doses of S. pneumoniae strains which is comparable to that achieved by PPV23. Mice immunized with DnaJ-ΔA146Ply produced significantly higher levels of anti-DnaJ IgG in serum and sIgA in saliva than DnaJ protein alone. The production of IL-17A is also striking in DnaJ-ΔA146Ply immunized mice. IL-17A KO mice didn't benefit from DnaJ-ΔA146Ply immunization in colonization experiments, and sIgA production was impaired in IL-17A KO mice. Collectively, our results indicate the mucosal adjuvant potential for ΔA146Ply and, without additional adjuvant, DnaJ-ΔA146Ply fusion protein is profound in immune stimulation and effective against pneumococcal challenges which is partially attributed to the IL-17A-mediated immune responses.