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

• Published in: PloS one Vol. 17; no. 4; p. e0266701
• Main Authors: Richardson, Jennifer R., Götz, Ralph, Mayr, Vanessa, Lohse, Martin J., Holthoff, Hans-Peter, Ungerer, Martin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.04.2022; Public Library of Science (PLoS)
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Antibodies; Authorship; Binding; Biology and Life Sciences; Blood; CD4 antigen; Complications and side effects; COVID-19 - prevention & control; Cytokines; Experiments; Flow cytometry; Health aspects; Humans; Humoral immunity; Immune response; Infections; Interleukin 2; Kinases; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Mutants; Mutation; Neutralization; Pandemics; Patient outcomes; Peptides; Proteins; Research and Analysis Methods; RNA, Viral; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike protein; T cells; T-Lymphocytes; Tumor necrosis factor-α; Vaccination; Vaccines; Viral diseases; Viral Envelope Proteins; Viral Vaccines; Viruses; γ-Interferon; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0266701

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). 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. 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.