Both Humoral and Cellular Immune Responses to SARS-CoV-2 are Essential to Prevent Infection: A Prospective Study in a Working Vaccinated Population from Southern France

Background: COVID-19 vaccines have significantly decreased the number severe cases of the disease but the virus circulation remains important and questions about the need of new vaccination campaigns remain unanswered.Methods: To better understand SARS-CoV-2-mediated immunity we assessed both B cell (measuring anti-Spike IgG titer and neutralization capacity) and T cell (measuring IFNγ release assay after specific SARS-CoV2 stimulation) responses to SARS-CoV-2 vaccination with or without virus encounter in a cohort of 367 working volunteers.Findings: Vaccinated individuals who had previously been infected had a stronger and more lasting immunity in comparison to vaccinated individuals naïve to infection whose immunity started to decline three months after vaccination. IFNγ release ≥ 0.285 IU/mL and anti-Spike IgG antibodies ≥ 244 BAU/mL were associated with a sufficient immune response following vaccination preventing future infections. Individuals with comorbidities had a lower chance of reaching the protective thresholds of T cell and B cell responses as identified in multivariate analysis.Interpretation: A combine B cell and T cell analysis of immune responses to determine protective thresholds after SARS-CoV-2 vaccination will allow us to identify individuals in need of a booster vaccine dose, particularly in comorbid subjects.Funding Information: This research was supported by grants from the Agence Nationale de la Recherche (FlashCOVID ANR-20-COVI-000) and Conseil Départemental des Alpes-Maritimes (CD06).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was reviewed and approved by a local institutional review committee (NCT04429594). During the inclusion visit, volunteers enrolled in the study signed a written informed consent in accordance with ethical and legal French policies.