Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expansion (p < 0.0001) and target T cell killing compared to controls when given s.c., and was ineffective orally. This study shows that spray drying is a suitable method for producing nanoparticulate vaccine formulations in dry powder form.