Infection caused by exposure to SARS CoV - 2 virus induces an antibody response against several structural proteins of the virus, among them nucleocapsid, spike, envelope, or, in turn, the Receptor Binding Domain (RBD); the first two have been the main target for use in diagnosis and monitoring of the evolution of the disease or vaccination process. The determination of antibodies against the disease called COVID-19 in mice was performed using a qualitative indirect ELISA assay to detect antibodies that were reactive to the Receptor Binding Domain (RBD) and Spike. In the standardization of the ELISA assay, concentrations of Spike and RBD proteins were tested in a range of 0.025 to 1 ug/well, and the concentrations of mouse serum as primary antibody in a range of 1/100 to 1/100000. The value of 0.2 ug/well was set as the Spike and RBD protein concentration for sensitization of high binding plates and 1/1000 as the optimal dilution of mouse serum for future assays. In conclusion, the indirect ELISA test can detect IgG antibodies from serum samples using recombinant Spike and RBD. Immunogenicity assays with PrS1 and PrRBD1 revealed these antigens’ ability to generate neutralizing antibody responses starting from the seventh-day post-immunization. These findings demonstrated that a single dose activated the immune response in the animal model. However, adding a second dose enhanced the immune response up to threefold and extended its duration for 42 days. Therefore, it is concluded that an immunization schedule with at least two doses is necessary.