Disclosed are compositions comprising a mesothelin protein and an adjuvant. Disclosed are compositions comprising a mesothelin protein, an adjuvant, and a second adjuvant. In some instances the adjuvant is cyclic dinucleotides (CDNs). Disclosed are compositions comprising a mesothelin protein, CDNs, and a squalene based oil-in-water emulsion. Disclosed are methods of treating cancer comprising administering to a subject a composition or vaccine, wherein the composition or vaccine comprises a mesothelin protein, an adjuvant, and a second adjuvant.