LAUSR

Background: To strategically develop preventive and therapeutic measures against coronavirus disease 2019 and its causative virus, SARS-CoV-2, it is critical to fully characterize immune response and sustained immune activation following viral infection and vaccination. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights into how we can optimize therapeutic and preventive care, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. Methods: We evaluated the expression of 29 cytokines and assessed their correlation with neutralizing potency. We further investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants of concern, and in vaccinated individuals. Results: Correlation analyses showed that the relationship between neutralizing activity and cytokine expression differed according to disease severity and viral strain. Furthermore, long-term longitudinal analyses revealed that post-vaccination neutralizing potential was more strongly associated with various cytokine expression levels in recovered patients than in naive individuals. Notably, we found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for one year. Conclusion: Our results showed that distinct immune responses occur depending on the viral strain suggesting that therapeutic options should be selected on a case-by-case basis. Furthermore, longitudinal analyses revealed biomarker candidates that correlated with repeated vaccination that may be applicable to therapies regulating specific immune responses and novel monoclonal antibodies.