SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes

Agerer, Benedikt; Koblischke, Maximilian; Gudipati, Venugopal; Smyth, Mark J.; Popa, Alexandra; Genger, Jakob-Wendelin; Endler, Lukas; Florian, David M.; Muehlgrabner, Vanessa; Lercher, Alexander; Gattinger, Pia; Torralba-Gombau, Ricard; Penz, Thomas; Faé, Ingrid; Wenda, S.; Traungott, Marianna; Walder, Gernot; Fischer, Gottfried; Hoepler, Wolfgang; Pawelka, Erich; Zoufaly, Alexander; Valenta, Rudolf; Bock, Christoph; Huppa, Johannes B.; Aberle, Judith H.; Bergthaler, Andréas

doi:10.1101/2020.12.18.423507

Cited by 13 publications

(9 citation statements)

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“…As a result, this mutation may allow a greater interaction between the spike protein and hACE2 ( 35 ). Thus genetic alterations may impair the host immune system's capacity to recognize and resist the virus ( 36 , 37 ). Certain mutations may enhance viral spread from cell to cell by fusion.…”

Section: Discussionmentioning

confidence: 99%

Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker

Shastri

Parikh

Aggarwal³

et al. 2021

Front. Med.

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Background: Post infection immunity and post vaccination immunity both confer protection against COVID-19. However, there have been many whole genome sequencing proven reinfections and breakthrough infections. Both are most often mild and caused by Variants of Concern (VOC).Methods: The patient in our study underwent serial COVID-19 RT-PCR, blood tests for serology, acute phase reactants, and chest imaging as part of clinical care. We interviewed the patient for clinical history and retrieved reports and case papers. We retrieved stored RT-PCR positive samples for whole genome sequencing (WGS) of SARS-CoV-2 from the patient's breakthrough infections and the presumed index case.Findings: The patient had three RT-PCR confirmed SARS-CoV-2 infections. Two breakthrough infections occurred in quick succession with the first over 3 weeks after complete vaccination with COVISHIELD and despite post-vaccination seroconversion. The first breakthrough infection was due to the Alpha variant and the second due to the Delta variant. The Delta variant infection resulted in hypoxia, hospitalization, and illness lasting seven weeks. Serial serology, acute phase reactants, and chest imaging supported WGS in establishing distinct episodes of infection. WGS established a fully vaccinated family member as the index case.Interpretation: The patient had an Alpha variant breakthrough infection despite past infection, complete vaccination, and seroconversion. Despite boosting after this infection, the patient subsequently had a severe Delta variant breakthrough infection. This was also a WGS proven reinfection and, therefore, a case of breakthrough reinfection. The patient acquired the infection from a fully vaccinated family member.

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Section: Discussionmentioning

confidence: 99%

Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker

Shastri

Parikh

Aggarwal³

et al. 2021

Front. Med.

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“…Selection of peptides from literature: T cell epitopes from COVID recovered convalescent patients' studies were selected from available vast literatures (14,15,17,28,29,30,32,38). The search was more for CD4+ epitopes as it was found CD8+ epitopes were heavily mutated (causing nonpersistent immunity) in different patients' samples (33). We mostly selected potent epitopes with definite secondary structures as per PDBsum.…”

Section: Methods: Clustal Omega Analyses Of Sars-1 and Sars-2 Spike S...mentioning

confidence: 99%

“…Also, more attention was given on CD4+ TCR epitopes than CD8+. Since the former sequences were found to be more stable than the other as per studies on patients (33). Finally, the designed sequence had 5 epitopes joined by linkers as cytoplasmic region.…”

Section: Introductionmentioning

confidence: 93%

De novodesign of anti-variant COVID-19 Vaccine

Goswami

Shankar

Gore

2022

Preprint

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Recent studies have shown the efficacy of hybrid COVID-19 vaccines using wild-type nucleocapsid (N) and Spike (S) protein. We upgrade this strategy by one step further using clinically proven spike protein (but with delta and post-delta omicron mutations) and nucleocapsid peptides conferring T-cell immunity. As per the latest research nucleocapsid peptides are perfect immunological replacement of nucleocapsid protein. Therefore, peptide linking strategy is pursued (economic for cellular biosynthesis than whole protein). One envelope peptide with potent T-cell response is also chosen. This peptide is also functionally indispensable for the virus. All these peptides were clustered in our designed cytoplasmic domain separated by non-immunogenic helical linkers. We also propose the idea of introduction of any T-cell peptide similar to other Human Corona Viruses (HuCoV) in these linker regions whenever required. In addition to COVID, the same approach can be applied for any emergency or even long-term unsolved outbreaks of Influenza, Dengue and West Nile Virus etc. In this era of novelty as presented by subunit and nucleic acid vaccines, multiepitope strategies like this can help to combat multiple diseases successfully in real time to give hope for better future.

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“…This auto-reactivity has been shown to correlate with the severity of clinical outcomes [ 21 ]. There is also evidence SARS-CoV-2 can subvert CD8+ T cell surveillance through escape mutations in MHCI-restricted viral epitopes [ 54 , 55 ]. The longer-term impacts on the immune system are yet unknown, but particularly in light of possible viral/antigenic persistence and the potential for reinfection, we should be concerned about the risk of lasting immune dysfunction and damage.…”

Section: Immune Dysregulationmentioning

confidence: 99%

Uncertainty around the Long-Term Implications of COVID-19

Desforges

Gurdasani

Hamdy³

et al. 2021

Pathogens

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 231 million people globally, with more than 4.7 million deaths recorded by the World Health Organization as of 26 September 2021. In response to the pandemic, some countries (New Zealand, Vietnam, Taiwan, South Korea and others) have pursued suppression strategies, so-called Zero COVID policies, to drive and maintain infection rates as close to zero as possible and respond aggressively to new cases. In comparison, European countries and North America have adopted mitigation strategies (of varying intensity and effectiveness) that aim primarily to prevent health systems from being overwhelmed. With recent advances in our understanding of SARS-CoV-2 and its biology, and the increasing recognition there is more to COVID-19 beyond the acute infection, we offer a perspective on some of the long-term risks of mutational escape, viral persistence, reinfection, immune dysregulation and neurological and multi-system complications (Long COVID).

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SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes

Cited by 13 publications

References 50 publications

Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker

Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker

De novodesign of anti-variant COVID-19 Vaccine

Uncertainty around the Long-Term Implications of COVID-19

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