T Cell Responses Correlate with Self-Reported Disease Severity and Neutralizing Antibody Responses Predict Protection against SARS-CoV-2 Breakthrough Infection

Objectives: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. Design and Methods: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. Results: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. Conclusion: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection.