SARS-CoV2 wild type and mutant specific humoral and T cell immunity is superior after vaccination than after natural infection

OBJECTIVE: We investigated blood samples from fully SARS-CoV2-vaccinated subjects and from previously positive tested patients up to one year after infection with SARS-CoV2, and compared short- and long-term T cell and antibody responses, with a special focus on the recently emerged delta variant (B.1.617.2). METHODS AND RESULTS: In 23 vaccinated subjects, we documented high anti-SARS-CoV2 spike protein receptor binding domain (RBD) antibody titers. Average virus neutralization by antibodies, assessed as inhibition of ACE2 binding to RBD, was 2.2-fold reduced for delta mutant vs. wild type (wt) RBD. The mean specific antibody titers were lower one year after natural infection than after vaccination; ACE2 binding to delta mutant vs. wt RBD was 1.65-fold reduced. In an additional group, omicron RBD binding was reduced compared to delta. Specific CD4+ T cell responses were measured after stimulation with peptides pools from wt, alpha, beta, gamma, or delta variant SARS-CoV2 spike proteins by flow cytometric intracellular cytokine staining. There was no significant difference in cytokine production of IFN-γ, TNF-α, or IL-2 between vaccinated subjects. T cell responses to wt or mutant SARS-CoV2 spike were significantly weaker after natural occurring infections compared to those in vaccinated individuals. CONCLUSION: Antibody neutralisation of the delta mutant was reduced compared to wt, as assessed in a novel inhibition assay with a finger prick blood drop. Strong CD4 T cell responses were present against wt and mutant SARS-CoV2 variants, including the delta (B.1.617.2) strain, in fully vaccinated individuals, whereas they were partly weaker 1 year after natural infection. Hence, immune responses after vaccination are stronger compared to those after naturally occurring infection, pointing out the need of the vaccine to overcome the pandemic.