Resistance to COVID-19 infection has been observed in health care workers and has been attributed to the presence of memory T cells that target the RNA polymerase in the RTC (replication transcription complex), thereby preventing infection. This makes RNA polymerase an important target for making a pan-coronavirus vaccine that will be effective against SARS-CoV-2 and its other variants of concern (VoC’s), but also against the family of Coronaviruses in general.
COVID-19 Pandemie is now almost 2 years old and has caused havoc among the world by disrupting world economy and halting the normal way of living. Millions have died and many more have been infected with the disease leading to high levels of morbidity. However, there have been instances where people have cleared the infection from the system so quickly that they didn’t test positive for the Virus or developed antibodies against it. This resistance has been attributed to the memory T cells-possibly those that are produced after exposure of the human system to such Viren.
In einer kürzlich in Nature von Swalding et al. veröffentlichten Studie wurden Blutproben von 60 Mitarbeitern des Gesundheitswesens entnommen, die einem hohen Risiko ausgesetzt waren COVID-19 due to their exposure, were examined and found out to be negative for the Virus and for the antibodies against the virus1. It is hypothesised that pre-existing memory T-cells, with cross-protective potential against SARS-CoV-2, expand in vivo to provide rapid viral clearance, thus aborting infection. These T cells are directed against the RNA-Polymerase im RTC (Replikations-Transkriptions-Komplex) und nicht in irgendeinem anderen Strukturprotein des Virus. Diese Gedächtnis-T-Zellen könnten bei den Mitarbeitern des Gesundheitswesens durch Kontakt mit anderen respiratorischen oder verwandten Coronaviren entstanden sein, obwohl es keine direkten Beweise dafür gibt. Es ist auch möglich, dass es andere umweltbedingte Auslöser gab, die zur Bildung dieser T-Zellen führten. Darüber hinaus zeigten diese seronegativen Personen auch einen Anstieg von IFI27, einem Protein, das auf eine fehlgeschlagene SARS-CoV-2-Infektion hinweist. IFI27 ist ein Interferon-alpha-induzierbares Protein, das bei Exposition gegenüber einer Vielzahl von Atemwegsviren, einschließlich SARS-CoV-2, überexprimiert wird. Dies kann auch für die virale Clearance bei Personen verantwortlich sein, die anderen Atemwegsviren vorexponiert und dann mit SARS-CoV-2 infiziert wurden.
The fact that the memory T cells are directed against the RNA polymerase (being the most conserved among the human Coronaviren that cause common cold and SARS-CoV-2), makes this enzyme an important target to develop a pan-Coronavirus vaccine that would not only be directed against SARS-CoV-2 and its other variants of concern (VoC’s) that have evolved as a result of mutations in the spike protein leading to more severe disease, but also against the family of Coronaviruses in general.
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Quelle:
Swadling, L., Diniz, MO, Schmidt, NM et al. Bereits vorhandene Polymerase-spezifische T-Zellen expandieren in abortivem seronegativem SARS-CoV-2. Natur (2021). https://doi.org/10.1038/s41586-021-04186-8
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