Introduction: Dengue is a disease caused by dengue virus and it is transmitted to humans by the bite of an infected mosquito, mainly Stegomyia aegypti. Currently dengue is a serious health problem for most tropical and subtropical countries, so the development of a vaccine against the disease has been considered a priority for the WHO. Objective: This work is aimed to obtain a higher yield of the recombinant protein DIIIC-4 (component of the vaccine candidate against dengue virus of the CIGB) by replacing the LB medium and the induction with IPTG for the autoinduction medium ZYB 5052. Material and Methods: This medium allow replace IPTG by α-lactose which is an economically more feasible. For studies performed in shaker, a factorial experimental design 32 was developed. The variables studied were the temperature and volume of medium, yielding the best results of protein of interest (287.04 mg/L) and cell growth (3.77 g/L dry weight) at 37°C in 100 mL of culture media. For studies in fermenters of 1.5 L of effective volume a factorial design 22 with a central point was conducted. The variables studied were the agitation speed and aeration. Results: The highest levels of protein of interest (472.75 mg/L) and bacterial growth (4.55 g/L dry weight) were obtained in conditions of increased agitation and aeration (700 min-1 and 1.5 vvm). Finally a kinetic of cell growth and expression level was conducted using a fermenter of 5 L of effective volume. The highest productivity was obtained 7 h after the inoculation of the culture (53.5 mg/Lh), reaching 374.51 mg/L of the protein DIIIC-4. Conclusions: This condition allowed increase the concentration levels of the protein DIIIC-4 more than 17 times and reduced more than 30 times the production costs, with respect to the previously obtained using the LB medium and IPTG.