Investigation On The Cellular Immune Response To COVID-19 Vaccine And Establishment Of Cellular Immune Response Studying Model

The outbreak of COVID-19 has developed into a COVID-19 pandemic globally since December 2019.Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)is the underlying cause of COVID-19.Many variants of SARS-Co V-2 emerged during the pandemic,including Delta(B.1.617.2)and Omicron(B.1.1.529).Multiple studies have shown that inflammatory responses in COVID-19 patients are characterized by high levels of chemokines and the continued release of immune factors such as IL-6.The cytokine storm generated after the deterioration of the inflammatory response is a determinant of the prognosis of COVID-19 disease and a driver of disease development.On the one hand,RNA of human peripheral blood mononuclear cells was collected and analyzed by transcriptome sequencing and bioinformatics at four time points: before inoculation with Sinovac inactivated virus vaccine,3-4 weeks after inoculation with 2 doses of vaccine,9-10 weeks after inoculation with 2 doses of vaccine and 4-5 weeks after inoculation with booster shot.It was found that two doses of sinovac vaccine and inoculation of sinovac booster vaccine could activate specific human antiviral immune defense pathway,and a large number of immune-related genes were activated in a short time.Consistent with existing reports,we also detected the secretion of large amounts of cytokines and chemokines.Our multi-point study showed that these strong immune activation responses declined over time,and that there were specific differences in immune responses between two doses of vaccine and booster shots.On the other hand,we stimulated co-cultured cell models containing mononuclear macrophages and lymphocytes with S1 recombinant proteins of SARS-Co V-2 wild-type(WT)and its mutant strains(Delta and Omicron)to simulate the immune cell microenvironment after SARS-Co V-2 infection.Through transcriptional sequencing analysis,we found that 24 h was the optimal time point for S1 protein to induce immune cell co-culture model.S1 protein of SARS-Co V-2wild type and its mutant strain could activate the immune cell co-culture model,and some immunomodulatory genes associated with virus infection were significantly upregulated.Interestingly,wild-type S1 elicited the strongest immune response,Delta S1 elicited a weaker immune response,and Omicron S1 elicited the fastest immune response.The results of this study provide cytological and molecular evidence for immune escape and hypertransmissibility of Delta and Omicron variants.This study also provides new ideas for vaccine development,immunoassay and drug development for COVID-19.