Liquid vaccine dosage forms have limited stability and require refrigeration during their manufacture, distribution and storage. In contrast, solid vaccine dosage forms, produced by for example spray drying, offer improved storage stability and reduced dependence on cold-chain facilities. This is advantageous for mass immunization campaigns for global public health threats, e.g., tuberculosis (TB), and offers cheaper vaccine distribution. The multistage subunit vaccine antigen H56, which is a fusion protein of the Mycobacterium tuberculosis (Mtb) antigens Ag85B, ESAT-6, and Rv2660, has been shown to confer protective efficacy against active TB before and after Mtb exposure in preclinical models, and it is currently undergoing clinical phase 2a testing. In several studies, including a recent study comparing multiple clinically relevant vaccine adjuvants, the T helper type 1 (Th1)/Th17-inducing adjuvant CAF01 was the most efficacious adjuvant for H56 to stimulate protective immunity against Mtb. With the long-term goal of designing a thermostable and self-administrable dry powder vaccine based on H56 and CAF01 for inhalation, we compared H56 spray-dried with CAF01 with the non-spray-dried H56/CAF01 vaccine with respect to their ability to induce systemic Th1, Th17 and humoral responses after subcutaneous immunization. Here we show that spray drying of the H56/CAF01 vaccine results in preserved antigenic epitope recognition and adjuvant activity of CAF01, and the spray-dried, reconstituted vaccine induces antigen-specific Th1, Th17 and humoral immune responses, which are comparable to those stimulated by the non-spray-dried H56/CAF01 vaccine. In addition, the spray-dried and reconstituted H56/CAF01 vaccine promotes similar polyfunctional CD4+ T-cell responses as the non-spray-dried vaccine. Thus, our study provides proof-of-concept that spray drying of the subunit vaccine H56/CAF01 preserves vaccine-induced humoral and cell-mediated immune responses. These results support our ongoing efforts to develop a thermostable, dry powder-based TB vaccine.