/sci/ - Science & Math

Omicron is known to largely resist potentially neutralizing Abs elicited by the current C-19 vaccines.
Diminished neutralization capacity of vaccinal Abs has been shown to substantially increase the affinity
of non-neutralizing vaccinal Abs for the N-terminal domain of S (S-NTD)
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351274/pdf/main.pdf]. In a previous contribution of
mine (https://trialsitenews.com/will-omicron-induce-herd-immunity-or-will-it-enable-sars-cov-2-to-
transition-into-variants-capable-of-potentiating-ade-in-vaccinees/), I’ve already suggested that these
non-neutralizing vaccinal Abs compete with relevant multi-specific innate Abs (i.e., IgMs) for binding to
SC-2 as in both cases binding is thought to involve multivalent binding interactions
(https://www.youtube.com/watch?v=wBm1BKL4zlg;
https://www.sciencedirect.com/science/article/pii/S0092867421006620).).

Since innate immune effector cells (IgM-secreting B1a cells) can recognize self-motifs displayed on
surface-expressed N-glycan patterns (such as displayed on the surface of glycosylated enveloped
viruses, including coronaviruses), innate IgM Abs are thought to mediate cytotoxic killing (via NK cells) of
virus-infected target cells at an early stage of infection and thereby contribute to sterilizing immunity. It
has been shown that in case of asymptomatic infection, an increase of innate/ natural CoV-reactive IgM
Abs and a high frequency of NK cells correlate with abrogation of infection and prevention of disease
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772470/pdf/fimmu-11-610300.pdf).).

Consequently, a high prevalence of elevated titers of non-neutralizing anti-S Abs (due to dominant
circulation of vaccine-resistant variants) is likely to suppress the capacity of highly vaccinated
populations to curtail viral transmission and hence, to achieve herd immunity.

Based on all the above, it is fair to conclude that ADEI in the URT as a result of poor virus neutralization
capacity would dramatically increase the amount of infectious SC-2 virions that are captured and
contained by DCs resident in the mucosal tissue at the portal of viral entry and would, therefore,
dramatically expand the reservoir the infectious virus can spill over from to different distant organs to
trigger ADED in the LRT once the trans infection barrier has been lifted. It is tempting to speculate that
O-glycosylation of the RBD is capable of lifting this barrier. The additional incorporation of one or more
amino acid mutations within a (highly) variable part of NTD that is adjacent to the enhancing domain is
thought to serve as an elegant and effective strategy for allowing O-glycosylated Newco variants to
restore optimal trans infectiousness and allow for ADEI-mediated ADED.
It is certainly conceivable that a higher O-glycosylation density on the RBD could even enhance trans
infection in vaccinees (i.e., by joining the cluster of N-glycans recruited by DC surface-expressed C-type
lectins and thus strengthening viral attachment to the URT-resident DCs) and even trans fusion between
virus-infected and not infected cells at distant target organs (i.e., by promoting the interaction between
oligomannoyslated glycans on S expressed at the surface of SC-2 infected cells and glycan-binding
determinants on uninfected neighboring cells). It is, therefore, reasonable to assume that site-specific
O-glycosylation on RBD would not only restore viral trans infection and trans fusion (i.e., by impeding
binding of the infection-enhancing Abs) but that it could even strengthen viral trans infection and trans
fusion and hence, enhance the likelihood of causing systemic C-19 disease.
It is, therefore, fair to posit that abundant O-linked glycosylation could make SC-2 highly virulent in
vaccinees and, therefore, make vaccinees highly susceptible to severe systemic disease.