Favorable vaccine-induced SARS-CoV-2–specific T cell response profile in patients undergoing immune-modifying therapies

Qui, Martin; Bert, Nina Le; Chan, Webber; Tan, Malcolm; Hang, Shou Kit; Hariharaputran, Smrithi; Sim, Jean Xiang Ying; Low, Jenny; Ng, Weiling; Wan, Wei Yee; Bertoletti, Antonio; Salazar, Ennaliza

doi:10.1172/jci159500

Cited by 25 publications

(35 citation statements)

References 44 publications

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“…Importantly, in vaccinees where their Spike-specific T cell response was significantly inhibited by the mutations present in Omicron, their combined vaccine-induced T cell response (Spike, Membrane and Nucleoprotein) was better preserved against Omicron (Figure 7C). The presence of multi-protein specific T cells in individuals vaccinated with inactivated virus can therefore provide them with a population of memory T cells more likely to tolerate the frequently found amino acid substitutions in Spike which can partially suppress the Spike-specific T cell response elicited by current Spike mRNA vaccines 42–48 . While the ability of Omicron to escape the full repertoire of Spike-specific T cells induced by mRNA vaccines occurs only in a minority of individuals (10-15%), immune escape can be substantial in particular for Spike-specific CD8 T cells 48 .…”

Section: Discussionmentioning

confidence: 99%

“…The presence of multi-protein specific T cells in individuals vaccinated with inactivated virus can therefore provide them with a population of memory T cells more likely to tolerate the frequently found amino acid substitutions in Spike which can partially suppress the Spike-specific T cell response elicited by current Spike mRNA vaccines [42][43][44][45][46][47][48] . While the ability of Omicron to escape the full repertoire of Spike-specific T cells induced by mRNA vaccines occurs only in a minority of individuals (10-15%), immune escape can be substantial in particular for Spike-specific CD8 T cells 48 .…”

Section: The Importance Of Eliciting a Multi-antigenic T Cell Respons...mentioning

confidence: 99%

“…The difference appears to be due to the different method of analysis utilized by us and by the group in Hong-Kong 26 . The AIM assay utilized by them and by many groups worldwide (including us 29,42,54 ) is a powerful cellular technique that can define the phenotype of peptide responsive T cells. It is equally well known that robust cytokine response of peptide responsive T cells can also activate other T cells in the vicinity in a bystander fashion without T cell receptor/epitope engagement [55][56][57] .…”

Section: The Importance Of Eliciting a Multi-antigenic T Cell Respons...mentioning

confidence: 99%

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Omicron reactive multi protein specific CD4 T cells defines cellular immune response induced by inactivated virus vaccines

Lim

Hang

Hariharaputran

et al. 2022

Preprint

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Unlike mRNA vaccines based only on the Spike protein, inactivated SARS-CoV-2 vaccines should induce a diversified T cell response recognizing distinct structural proteins. Here we performed a comparative analysis of SARS-CoV-2 specific T cells in healthy individuals following vaccination with inactivated SARS-CoV-2 or mRNA vaccines. Relative to Spike mRNA vaccination, inactivated vaccines elicited a lower magnitude of Spike-specific T cells, but the combined Membrane, Nucleoprotein and Spike specific T cell response was quantitatively comparable to the sole Spike T cell response induced by mRNA vaccines, and they efficiently tolerate the mutations characterizing the Omicron lineage. However, this multi-protein specific T cell response was not mediated by a coordinated CD4 and CD8 T cell expansion but by selected priming of CD4 T cells. These findings can help in defining the role of CD4 and CD8 T cells in the efficacy of the different vaccines to control severe COVID-19 after Omicron infection.

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Section: Discussionmentioning

confidence: 99%

Section: The Importance Of Eliciting a Multi-antigenic T Cell Respons...mentioning

confidence: 99%

Section: The Importance Of Eliciting a Multi-antigenic T Cell Respons...mentioning

confidence: 99%

See 1 more Smart Citation

Omicron reactive multi protein specific CD4 T cells defines cellular immune response induced by inactivated virus vaccines

Lim

Hang

Hariharaputran

et al. 2022

Preprint

Self Cite

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“…Production of neutralizing antibody was evidenced even when they were tested against virus variants ( 65 ). Poor impact of variants on immune response to mRNA vaccines in IBD patients seems confirmed by the evidence that in subjects receiving antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing two-dose COVID-19 mRNA vaccination a favorable profile of vaccine-induced T cell responses was found, despite they were infected by the omicron variant ( 74 ).…”

Section: Immune Response Of Patients With Inflammatory Bowel Disease ...mentioning

confidence: 90%

Risks of SARS-CoV-2 Infection and Immune Response to COVID-19 Vaccines in Patients With Inflammatory Bowel Disease: Current Evidence

Esposito

Caminiti

Giordano³

et al. 2022

Front. Immunol.

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Inflammatory bowel diseases (IBD), including Crohn’s disease, ulcerative colitis, and unclassified inflammatory bowel disease, are a group of chronic, immune mediated conditions that are presumed to occur in genetically susceptible individuals because of a dysregulated intestinal immune response to environmental factors. IBD patients can be considered subjects with an aberrant immune response that makes them at increased risk of infections, particularly those due to opportunistic pathogens. In many cases this risk is significantly increased by the therapy they receive. Aim of this narrative review is to describe the impact of SARS-CoV-2 infection and the immunogenicity of COVID-19 vaccines in patients with IBD. Available data indicate that patients with IBD do not have an increased susceptibility to infection with SARS-CoV-2 and that, if infected, in the majority of the cases they must not modify the therapy in place because this does not negatively affect the COVID-19 course. Only corticosteroids should be reduced or suspended due to the risk of causing severe forms. Furthermore, COVID-19 seems to modify the course of IBD mainly due to the impact on intestinal disease of the psychological factors deriving from the measures implemented to deal with the pandemic. The data relating to the immune response induced by SARS-CoV-2 or by COVID-19 vaccines can be considered much less definitive. It seems certain that the immune response to disease and vaccines is not substantially different from that seen in healthy subjects, with the exception of patients treated with anti-tumor necrosis factor alone or in combination with other immunosuppressants who showed a reduced immune response. How much, however, this problem reduces induced protection is not known. Moreover, the impact of SARS-CoV-2 variants on IBD course and immune response to SARS-CoV-2 infection and COVID-19 vaccines has not been studied and deserves attention. Further studies capable of facing and solving unanswered questions are needed in order to adequately protect IBD patients from the risks associated with SARS-CoV-2 infection.

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“…Data on patients with inflammatory bowel disease (IBD) treated with high doses of systemic corticosteroids, infliximab, or infliximab and immunomodulators showed that they present a blunted response to the anti-SARS-CoV-2 vaccination [ 133 ]. However, a study on humoral and spike-specific T cell responses in patients with IBD who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing two-dose COVID-19 mRNA vaccination showed that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also was sustained at a higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy [ 134 ].…”

Section: Immune Response To Sars-cov-2 Vaccinationmentioning

confidence: 99%

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences

et al. 2022

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

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Favorable vaccine-induced SARS-CoV-2–specific T cell response profile in patients undergoing immune-modifying therapies

Cited by 25 publications

References 44 publications

Omicron reactive multi protein specific CD4 T cells defines cellular immune response induced by inactivated virus vaccines

Omicron reactive multi protein specific CD4 T cells defines cellular immune response induced by inactivated virus vaccines

Risks of SARS-CoV-2 Infection and Immune Response to COVID-19 Vaccines in Patients With Inflammatory Bowel Disease: Current Evidence

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences

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