Can B cell‐deficient patients rely on <scp>COVID</scp>‐19 vaccine‐induced T‐cell immunity?

Shree, Tanaya

doi:10.1111/bjh.18210

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Previous findings showed that the frequency of the MAIT cell compartment positively correlates with the anti-SARS-CoV-2 IgG levels in BNT162b2 mRNA vaccinated subjects ( 28 ). Since some SARS-CoV-2 infected or vaccinated individuals may elicit a cellular sensitization without evidence of the virus-specific Ab production ( 41 , 42 ), we performed a comparative analysis between the concentrations of anti-SARS-CoV-2 IgG and the level of the MAIT-associated TNF in our dataset. Importantly, we found an overlapping trend between these two parameters that showed the highest magnitude early after the vaccine boost in relation to their pre-vaccine status ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination

et al. 2023

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IntroductionHigher frequencies of mucosal-associated invariant T (MAIT) cells were associated with an increased adaptive response to mRNA BNT162b2 SARS-CoV-2 vaccine, however, the mechanistic insights into this relationship are unknown. In the present study, we hypothesized that the TNF response of MAIT cells supports B cell activation following SARS-CoV-2 immunization.MethodsTo investigate the effects of repeated SARS-CoV-2 vaccinations on the peripheral blood mononuclear cells (PBMCs), we performed a longitudinal single cell (sc)RNA-seq and scTCR-seq analysis of SARS-CoV-2 vaccinated healthy adults with two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Collection of PBMCs was performed 1 day before, 3 and 17 days after prime vaccination, and 3 days and 3 months following vaccine boost. Based on scRNA/TCR-seq data related to regulatory signals induced by the vaccine, we used computational approaches for the functional pathway enrichment analysis (Reactome), dynamics of the effector cell-polarization (RNA Velocity and CellRank), and cell-cell communication (NicheNet).ResultsWe identified MAIT cells as an important source of TNF across circulating lymphocytes in response to repeated SARS-CoV-2 BNT162b2 vaccination. The TNFhigh signature of MAIT cells was induced by the second administration of the vaccine. Notably, the increased TNF expression was associated with MAIT cell proliferation and efficient anti-SARS-CoV-2 antibody production. Finally, by decoding the ligand-receptor interactions and incorporating intracellular signaling, we predicted TNFhigh MAIT cell interplay with different B cell subsets. In specific, predicted TNF-mediated activation was selectively directed to conventional switched memory B cells, which are deputed to high-affinity long-term memory.DiscussionOverall, our results indicate that SARS-CoV-2 BNT162b2 vaccination influences MAIT cell frequencies and their transcriptional effector profile with the potential to promote B cell activation. This research also provides a blueprint for the promising use of MAIT cells as cellular adjuvants in mRNA-based vaccines.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination

et al. 2023

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“…our 5 x 10 4 TCID 50 ), and used a variant of SARS-CoV-2 that is not pathogenic in wild type mice ( 6 ). In addition to specific antibody responses, COVID-19 vaccinees and convalescent patients possess SARS-CoV-2 specific CD8 + and CD4 + T cells, suggesting the contribution of the T cell compartment to the adaptive immunity to COVID-19 ( 29 ), and clinical findings have revealed vaccine-induced T cell responses in B cell-deficient patients ( 30 ). It has also been reported that vaccination by WA (Wuhan) Spike in a mouse model failed to produce antibodies fully capable of neutralizing the SA (Beta) variant of SARS-CoV-2, yet immunized mice were protected against Beta strain challenge ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta

et al. 2023

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Licensed COVID-19 vaccines ameliorate viral infection by inducing production of neutralizing antibodies that bind the SARS-CoV-2 Spike protein and inhibit viral cellular entry. However, the clinical effectiveness of these vaccines is transitory as viral variants escape antibody neutralization. Effective vaccines that solely rely upon a T cell response to combat SARS-CoV-2 infection could be transformational because they can utilize highly conserved short pan-variant peptide epitopes, but a mRNA-LNP T cell vaccine has not been shown to provide effective anti-SARS-CoV-2 prophylaxis. Here we show a mRNA-LNP vaccine (MIT-T-COVID) based on highly conserved short peptide epitopes activates CD8+ and CD4+ T cell responses that attenuate morbidity and prevent mortality in HLA-A*02:01 transgenic mice infected with SARS-CoV-2 Beta (B.1.351). We found CD8+ T cells in mice immunized with MIT-T-COVID vaccine significantly increased from 1.1% to 24.0% of total pulmonary nucleated cells prior to and at 7 days post infection (dpi), respectively, indicating dynamic recruitment of circulating specific T cells into the infected lungs. Mice immunized with MIT-T-COVID had 2.8 (2 dpi) and 3.3 (7 dpi) times more lung infiltrating CD8+ T cells than unimmunized mice. Mice immunized with MIT-T-COVID had 17.4 times more lung infiltrating CD4+ T cells than unimmunized mice (7 dpi). The undetectable specific antibody response in MIT-T-COVID-immunized mice demonstrates specific T cell responses alone can effectively attenuate the pathogenesis of SARS-CoV-2 infection. Our results suggest further study is merited for pan-variant T cell vaccines, including for individuals that cannot produce neutralizing antibodies or to help mitigate Long COVID.

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“…The robust B cells and T follicular helper cell responses stimulated by COVID-19 vaccination contribute to the production of antibodies, which provide remarkable protection against SARS-CoV-2 infection, and reduction in hospitalization and death [ 13 , 14 ]. Notably, the depletion of B cells with anti-B antibodies in Non-Hodgkin lymphoma and chronic lymphocytic leukemia patients has been shown to weaken the humoral response and the production of Spike-specific antibodies following vaccination, increasing the risk of breakthrough infections [ 15 , 16 , 17 ]. Effector T and B cell responses following infection or vaccination also contribute to the subsequent development of specific immunological memory [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Natural Killer Cells Do Not Attenuate a Mouse-Adapted SARS-CoV-2-Induced Disease in Rag2−/− Mice

Ellsworth,

Wang,

Katz

et al. 2024

Viruses

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This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 (K18-hACE2) mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected K18-hACE2 mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as Rag2−/− showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in Rag2−/− mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19.

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Can B cell‐deficient patients rely on COVID‐19 vaccine‐induced T‐cell immunity?

Cited by 4 publications

References 31 publications

Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination

Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination

A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta

Natural Killer Cells Do Not Attenuate a Mouse-Adapted SARS-CoV-2-Induced Disease in Rag2−/− Mice

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