> Pseudo’neutralization occurs when the once-neutralizing Abs are boosted due to vaccine breakthrough infection (VBTI) caused by circulating variants that have largely evaded the protective neutralizing Abs induced by Covid-19 (C-19) vaccines. Boosting results in a significant increase in the titer of these Abs, which therefore acquire the capacity to hinder viral infection by hydrophilizing virus-Ab complexes. However, due to their low binding affinity, especially after maturation into isotype-switched IgG4 Abs, these Abs will rapidly lose their infection-inhibiting (i.e., ‘pseudo’neutralizing) capacity, thereby exerting large-scale suboptimal immune pressure on viral infectiousness in highly C-19 vaccinated populations. This collective immune pressure contributes to the co-emergence and co-circulation of new immune escape variants, which are currently causing large-scale repeated VBTIs in highly C-19 vaccinated populations.

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