preprints.org > biology and life sciences > virology > doi: 10.20944/preprints202212.0155.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 6 December 2022 / Approved: 8 December 2022 / Online: 8 December 2022 (10:02:23 CET)
Version 2 : Received: 20 December 2022 / Approved: 21 December 2022 / Online: 21 December 2022 (02:31:00 CET)
Version 3 : Received: 18 February 2023 / Approved: 20 February 2023 / Online: 20 February 2023 (02:28:09 CET)
Version 4 : Received: 20 February 2023 / Approved: 21 February 2023 / Online: 21 February 2023 (02:38:38 CET)

The COVID-19 pandemic and the recently-emerged highly transmissible SARS-CoV-2 Omicron variants have increased the demands for novel immunising and therapeutic approaches to protect the lives of patients with significant co-morbidities. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of the novel SARS-CoV-2 variants on people with serious co-morbidities, and there is still a dilemma of how we could prevent potentially catastrophic effects of future pandemics upon the human race. And the concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to go undetected during the first stages of infection by means of capping the 5' end of their genetic material, reducing the synthetic rate of Type I and Type III Interferons, temporarily inhibiting the apoptotic pathways of infected cells to facilitate a rapid viral replication, and inhibiting antigenic presentation. Type I and III Interferon-based viral immune evasion may be primarily associated with a delayed clearance of the viral load. Evidence also shows that the SARS-CoV-2 spike protein inhibited the V(D)J antibody gene rearrangement in developing B-lymphocytes, as well as diverse important cellular processes of DNA repair by downregulating the BRCA1 and 53BP1 genes. Furthermore, most traditional methods of vaccination do not particularly boost mucosal immunity and as a result, there is a visible gap that viruses can easily fill in, which implicates a reduced stimulation of a mucosal plasma cell production. Serum plasma antibodies do not cross the nasal epithelium and hence, offer little protection against mucosal inflammation, unlike the antibodies produced by mucosal plasma cells. We acknowledge the existence of a significant challenge to stimulate mucosal immune responses due to the high complexity of its structure-function axis. Nevertheless, over the past half century, numerous scientists developed ways of immunisation and early treatment worldwide that generally showed outstanding levels of success and insignificant risks of adverse events. An important example implicates the administration of human interferons I and III into the nasal mucosa to simulate local infection and train the innate immune system to robustly become activated and transmit essential signals before viruses silence it. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses had generated long-term evolutionary responses to deeply tackle the ability of the complex human immune system to neutralise viruses during the first stages of cellular infection. It is until the scientific community realises this that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades.

covid-19; pandemic; immune evasion; first-line immunity; viral evolution; interferon; vaccinology

Biology and Life Sciences, Virology

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