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Background: A safe and effective adjuvant plays an important role in the development of a vaccine.However,adjuvants licensed for administration in humans remain limited.Here,for the first time,we developed a novel combination adjuvant alum-polysaccharide-HH2(APH)with potent immunomodulating activities,consisting of alum,polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2.Methods: The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models.We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH(NAPH)vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice.Cell-mediated and antibody-mediated immune responses were evaluated.Results: The APH complex significantly promoted antigen uptake,maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α,MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components.Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models.In addition,passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16.Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity.Therefore,NAPH vaccination effectively stimulated innate immunity,and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma.Conclusions: Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth.