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@ 2023-12-30 18:54:00
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  1. Vaccine-mediated protection against severe disease is no longer provided by the neutralizing capacity of vaccine-induced neutralizing antibodies (Abs) but by new, broadly cross-reactive Abs of low intrinsic affinity that have been generated following VBTI (vaccine breakthrough infection)- or mRNA vaccine-mediated immune refocusing in highly vaccinated populations.

  2. Abs with low intrinsic affinity for the Spike (S) protein promote viral aggregation.

  3. Enhanced uptake of viral aggregates by antigen-presenting cells (APCs) causes hyperactivation of antigen-presenting cells (APCs) and thereby activates cytotoxic T lymphocytes (CTLs) instead of recalling previously vaccine-primed CD4+ T helper memory cells.

  4. Lack of cognate CD4+ T help will prevent assistance to recalling B cells producing non-neutralizing Abs (NNAbs) that are directed at repetitive patterns of a conserved antigenic domain (the so-called 'enhancing site') comprised within the N-terminal domain of the S protein (S-NTD).

  5. Lack of recall of these NNAbs cause their concentration in the blood and peripheral barriers to decline below the threshold required for these Abs to inhibit viral trans infection.

  6. Inhibition of viral trans infection prevents cellular trans fusion and dissemination of the virus to one or more distal organs and thereby prevents severe/systemic C-19 disease.

  7. Suboptimal population-level immune pressure exerted on viral trans infection will lead to immune selection pressure on viral trans infection.

  8. Immune selection pressure on viral trans infection will prompt natural selection and propagation of new variants that have the capacity to overcome NNAb-mediated inhibition of viral trans infection in all of a highly C-19 vaccinated population. These variants have therefore the capacity to become highly virulent in C-19 vaccinees.

  9. This trend cannot be reversed by vaccination as aggregation of highly infectious circulating virus by Abs with low intrinsic binding affinity for S protein is promoted by inevitable re-exposure of vaccinated individuals.

  10. In conclusion: Due to immune refocusing triggered by early Omicron variants, immune evasion is no longer solely a matter of enhanced S protein's binding affinity to the hACE2 receptor and other alterations in viral molecular structures. Immune evasion is now mainly determined by evolving modifications in the interaction of the circulating virus with the elicited adaptive immune response in highly COVID-19 vaccinated populations.


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