Oral and Intranasal Immunization with Recombinant Food-Grade Lactococcus Lactis Expressing High Conserved Region of SARS-CoV-2 Spike Protein Triggers Immunity Responses in Mice

Abstract Background: The COVID-19 pandemic began at the end of 2019 in Wuhan, China, and has spread throughout the world until mid-2021. Thus far, no specific therapy has been found for the coronavirus family. Vaccination still becomes the most effective prevention of pathogenic infections, including viral infections. However, little data show that this vaccination can protect against SARS-CoV-2 virus for a long time. Thus, revaccination needs to be regularly carried out to prevent the occurrence of COVID-19. Vaccination by injection is invasive, and it becomes one of the reasons people refuse to get revaccinated. Therefore, we developed a less invasive vaccine based on oral or nasal administration. The gene encoding the high conserved region (HCR) spike protein was inserted into pNZ8149 and expressed in L. lactis NZ3900. Results: The results of nasal and oral administration in experimental animals showed that L. lactis carrying the HCR gene could induce a humoral immune response, as indicated by an increasing IgG and IgA against SARS-CoV-2 (IgG/IgA-SARS-CoV-2) levels and the lymph cell population after nasal and oral vaccination in mice (p<0.05). Conclusion: This study shows promising results that can be developed into a less invasive alternative to nasal and oral vaccination.