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

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)....

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Published inPloS 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
LanguageEnglish
Published United States Public Library of Science 25.04.2022
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Abstract 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.
AbstractList 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-[gamma], TNF-[alpha], 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.
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-[gamma], TNF-[alpha], 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.
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.
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.
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).OBJECTIVEWe 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.METHODS AND RESULTSIn 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.CONCLUSIONAntibody 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.
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.
Audience Academic
Author Richardson, Jennifer R.
Holthoff, Hans-Peter
Ungerer, Martin
Götz, Ralph
Lohse, Martin J.
Mayr, Vanessa
AuthorAffiliation ISAR Bioscience, Planegg, Germany
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, UNITED STATES
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  givenname: Martin J.
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35468147$$D View this record in MEDLINE/PubMed
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– notice: 2022 Richardson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Competing Interests: The fact that all authors are employees of the non-profit ISAR Bioscience Institute which formally acts as a biotech company does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors or ISAR do not impose any restrictions on sharing of data and/or materials.
HPH and MU shared senior authorship on this work.
ORCID 0000-0002-5198-3399
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Snippet We investigated blood samples from fully SARS-CoV2-vaccinated subjects and from previously positive tested patients up to one year after infection with...
Objective We investigated blood samples from fully SARS-CoV2-vaccinated subjects and from previously positive tested patients up to one year after infection...
Objective We investigated blood samples from fully SARS-CoV2-vaccinated subjects and from previously positive tested patients up to one year after infection...
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SubjectTerms 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
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Title SARS-CoV2 wild type and mutant specific humoral and T cell immunity is superior after vaccination than after natural infection
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