T Cells Targeting SARS-CoV-2: By Infection, Vaccination, and Against Future Variants

Nguyen, Thi H. O.; Cohen, Carolyn A.; Rowntree, Louise C.; Bull, Maireid B.; Hachim, Asmaa; Kedzierska, Katherine; Valkenburg, Sophie A.

doi:10.3389/fmed.2021.793102

Cited by 26 publications

(24 citation statements)

References 104 publications

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“…The strength and maintenance of IFN-γ-producing T cells and total and neutralizing antibodies from 1 to 6 months post-vaccination were significantly higher in SARS-CoV-2 recovered compared to naïve individuals. Recovered subjects present what is called “hybrid immunity”, which is developed by the combination of vaccination and natural infection, and results in more potent and long-lived immune response ( 50 ), partly due to a wider breadth for T cells and antibodies ( 51 , 52 ). In fact, in our cohort none of the recovered subjects had a breakthrough infection during the 12-month follow up period.…”

Section: Discussionmentioning

confidence: 99%

Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses

et al. 2022

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BackgroundSARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity.ObjectiveTo determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection.Methods12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve.ResultsPeak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections.ConclusionBooster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.

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Section: Discussionmentioning

confidence: 99%

Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses

et al. 2022

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“…By design, modern mRNA vaccines drive transient expression of protein antigens accessible to MHC class I processing machinery. Since CD8+ T cells are important effector cells that expand in the early protection window after prime SARS-CoV-2 spike mRNA vaccination [ 67 ] and maintain recognition of variants of concern due to epitope conservation [ 68 ], it might also be beneficial to coadministrate the DIs together with SARS-CoV-2-spike mRNA vaccines.…”

Section: Discussionmentioning

confidence: 99%

Inhibitors of Deubiquitinating Enzymes Interfere with the SARS-CoV-2 Papain-like Protease and Block Virus Replication In Vitro

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Rauch

et al. 2022

Viruses

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The ubiquitin proteasome system (UPS), particularly its deubiquitinating enzymes (DUBs), play a key role in the replication cycle of coronaviruses. The SARS-CoV-2 papain-like protease (Plpro) is known to process the viral polyproteins to form the replicase transcriptase complex and to counteract the host viral response. Recently, it was shown that this viral protease can also act as a deubiquitinating enzyme. In this study, we demonstrate that certain DUB-Inhibitors (DIs) interfere with SARS-CoV-2 replication. The DIs PR-619 and HBX41108 restrict SARS-CoV-2 in both Vero B4 and human Calu-3 lung cells where cells were infected with a Multiplicity of Infection (MOI) of 0.02. An in vitro protease assay using recombinant Plpro and Amido-4-methylcoumarin (AMC)-conjugated substrate revealed that PR-619 and HBX41108 are able to block the protease at concentrations where the interventions restricted virus replication. In contrast, DIs that do not inhibit Plpro had no influence on virus replication, which indicated that the protease might be at least one major target. Future vertical studies that would gain more insights into the mechanisms of how DUBs effect the replication of SARS-CoV-2 will further validate them as a potential therapeutic target.

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“…Moreover, no anti-N antibodies were detected consequently to infection at this time and only low antibody levels were found in P1, suggesting that these immune responses measured early after infection were a good reflection of the previous vaccine response. Finally, we did not explore de novo T cell responses induced by infection (particularly against nucleocapsid and membrane proteins) that may also have shortened the time of viral clearance and tempered disease severity, along with anti-S T cell recall responses (12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Evolution of Humoral and Cellular Immunity in Two COVID-19 Breakthrough Infections After BNT162b2 Vaccine

et al. 2022

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BackgroundSARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized.MethodsWe analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally.ResultsThe first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4+IL-2+ cells) and CD8 effector response (CD8+IFNγ+ cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection.ConclusionsAn analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies.

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T Cells Targeting SARS-CoV-2: By Infection, Vaccination, and Against Future Variants

Cited by 26 publications

References 104 publications

Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses

Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses

Inhibitors of Deubiquitinating Enzymes Interfere with the SARS-CoV-2 Papain-like Protease and Block Virus Replication In Vitro

Case Report: Evolution of Humoral and Cellular Immunity in Two COVID-19 Breakthrough Infections After BNT162b2 Vaccine

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