The Dynamic Changes Of Immune Responses After Inoculation With An Inactivated SARS-CoV-2 Vaccine

Background and ObjectiveSevere Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)infection has been considered a public health emergency of international concern.Vaccination to form a herd immunity barrier is an effective means to prevent SARS-CoV-2 pandemic.Inactivated SARS-CoV-2 vaccine is commonly inoculated in China.Blood neutralizing antibody titers are mostly used as evaluation criteria in experiments studying vaccine effectiveness and immune effects,however,studies on lymphocyte subsets and their dynamic characteristics are not yet available.Therefore,this study focused on investigating the dynamic changes in innate and adaptive immunity in the human body after inoculation with an inactivated SARS-CoV-2 vaccine.Methods25 healthcare workers were inoculated with an inactivated SARS-CoV-2 vaccine and the peripheral blood mononuclear cells(PBMC)were taken from them before inoculation,1 week and 4 weeks after the first dose,as well as 1 week and 4 weeks after the second dose.These samples were subjected to flow cytometry to detect the frequency of follicular helper T cells(Tfh),follicular cytotoxic T cells(Tfc),naive T cells(Tn)and different memory and effect subsets(Tcm,Tem and Temra)in CD4+T cells and CD8+T cells,as well as the expressions of CD69 and PD-1 in each subsets and the capacity of follicular helper T cells and follicular cytotoxic T cells to secret cytokines IL-2,IL-21,IFN-y and TNF-α.Then,we explored the frequency of B cell subsets(immature B cells,naive B cells,plasmablast,memory B cells,plasma cells)and the expression of CD80 and CD71 in each subsets,in addition to the capacity of B cell to secret cytokines including IL-10,IL-6,IFN-y and TNF-α.The frequency of NK cells and their subsets(CD56bright CD16-NK cells,CD56dim CD16+NK cells,CD56dimCD16-NK cells)as well as the expression of activation receptors NKp46 and NKG2D and the capacity to secret CD 107a and IFN-y were also detected.Lastly,AntiRBD IgM,anti-RBD IgG and anti-N IgG titers were detected.ResultsIn this study,we discovered that the ability of follicular cytotoxic T cells to secrete TNF-α was significantly enhanced,and the proportions of follicular helper T cells,central memory CD4+T cells,and terminally differentiated effector memory CD4+T cells expressing PD-1 reduced strongly after inactivated SARS-CoV-2 vaccine.These results suggested that the CD4+T cell subsets might be activated after inactivated SARS-CoV-2 vaccine.In contrast,the proportion of naive CD8+T cells,central memory CD8+T cells,and terminally differentiated effector memory CD8+T cells expressing PD-1 was increased.Moreover,after the second dose of vaccine,the proportion of immature B cells,naive B cells,and memory B cells expressing CD80 decreased significantly,whereas the enhanced ability of B cells to secrete TNF-α,as well as the significantly elevated Anti-RBD IgM,anti-RBD IgG and anti-N IgG titers.The capacity of CD56dimCD16-NK cells to secrete IFN-γ and CD 107a enhanced robustly after the second dose of inactivated SARS-CoV-2 vaccine and the proportions of NK cells,CD56dimCD16+NK cells,and CD56dimCD16-NK cells expressing NKG2D also increased significantly.ConclusionsThese findings demonstrate that two doses of inactivated SARS-CoV-2 vaccine induce strong innate and adaptive immunity.The lymphocyte phenotypes and secreted cytokines are extensively affected by inactivated SARS-CoV-2 vaccine,which greatly contributes to our understanding of the dynamic changes in immune responses after inactivated SARS-CoV-2 vaccine.