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.

COVID-19 vaccines have significantly decreased the number of severe cases of the disease, but the virus circulation remains important, and questions about the need of new vaccination campaigns remain unanswered. The individual's protection against SARS-CoV-2 infection is most commonly measured by the level and the neutralizing capacity of antibodies produced against SARS-CoV-2. T cell response is a major contributor in viral infection, and several studies have shown that cellular T cell response is crucial in fighting off SARS-CoV-2 infection. Actually, no threshold of protective immune response against SARS-CoV2 infection has been identified. 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. Vaccinated individuals who had previously been infected had a stronger and more lasting immunity in comparison to vaccinated individuals naive to infection whose immunity started to decline 3 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. A combined 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.