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

Abstract

Objective: We investigated blood samples from fully SARS-CoV2-vaccinated subjects and from 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. wt RBD. Specific CD4+ T cell responses as measured using stimulation with peptides representing wt or alpha, beta, gamma and delta variant SARS-CoV2 entire spike proteins by flow cytometric intracellular cytokine staining, did not differ significantly between vaccinees. One year post infection in one of the earliest SARS-CoV2 populations in the Western world, mean specific antibody titers were lower than in vaccinees; ACE2 binding to delta mutant vs. wt RBD was 1.65-fold reduced. T cell responses, especially interferon gamma expression, to mutant SARS-CoV2 spike were significantly reduced compared to those in vaccinees. Conclusion: Strong T cell responses occurred for wildtype and mutant SARS-CoV2 variants, including delta (B.1.617.2), in fully vaccinated individuals, whereas they were partly reduced 1 year after natural infection. Antibody neutralisation of delta mutant was reduced compared to wt, as assessed in a novel inhibition assay with a finger stick drop of blood. 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.