The discussion of the phase 1/2 clinical studies for the rAd26 and rAd5 vector-based COVID-19 vaccine highlighted that the heterologous prime-boost immunization is safe and effectively elicits an immune response without serious adverse effects. The vaccine produced strong humoral and cellular (T-cell) immune responses, including higher rates of CD8+ T cells and increased interferon-gamma secretion. Although neutralizing antibody levels were lower than those elicited by the ChAdOx1 vaccine, they were comparable to titers in patients recovered from COVID-19. Furthermore, the heterologous prime-boost strategy successfully overcame the immune response typically formed against viral vector components. Further studies are required to test the vaccine in older and at-risk populations.