We will never end this COVID PANDEMIC if we can't reduce infectious pressure on the spike! Omicron is NOT the gift we thought; waves do not rejoin baseline & infectious pressure is constantly high

by Paul Alexander

The interplay between the infectious pressure by the virus & the population immune pressure (mounting vaccinal antibodies) is not studied and understood; we have damaged the viral-host ecosystem

We must reduce the infectious pressure. If we do not, the virus will find a way to. Could this via reduced population?

GVB proposes massive anti-viral chemoprophylaxis campaigns and a complete stop of the vaccine. Chemoprophylaxis IMO is key but the governments will not do this. This is the problem. Yet we have to reduce the infectious pressure and thus reduced risk of infectious and/or virulent variants emerging.

Once there is elevated infection circulating, the sub-optimal imperfect ‘immature’ not fully developed vaccinal immune pressure (that also is a mismatch to the present omicron spike and not the vaccine’s Wuhan pike) emerging from the population due to mass vaccination, cannot eliminate the virus, and thus bumping up against the viral pressure (high levels of virus), will drive the strongest most infectious hardiest variants to overcome the sub-optimal immune pressure. These variants would be selected and become enriched in the environment.

A key consideration: The higher the resistance to the neutralizing vaccinal antibodies (e.g. using a Wuhan strain vaccine while the predominant variant is omicron; the omicron virus resists the vaccinal Abs made to Wuhan), the stronger the non-neutralizing antibodies will bind to the spike.

The more pressure we place on the virus’s spike (binding but not eliminating the virus yet increasing/enhancing infectiousness to the vaccinated persons), the more susceptible the population becomes for infection and re-infection.

By boosting, we boost the non-neutralizing sub-optimal Abs, and we place extra immune pressure on the virus as we boost the non-neutralizing antibodies. When non-neutralizing antibodies increase due to boosting and strongly bind to spike, the vaccinee also becomes more susceptible to the virus due to the binding of the non-neutralizing Abs to the virus that enhances (facilitates) infection in the vaccinated person. We see this is emerging strong research as to the role of enhancing, facilitating (non-neutralizing) antibodies in causing infection in the vaccinated. Yahi et al. looked at Delta etc. but very instructive to the now Omicron sub-variants.

For example, good evidence of this is shown by Yahi et al. Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination?…showed that the Abs (non-neutralizing) by binding to the virus, cause enhanced infectiousness causing ADE of infection. The non-neutralizing Abs have an increased affinity for the spike as the neutralizing Abs do not work on the present Delta in the study (originally for the Wuhan). We even see indications of original antigenic sin (OAS) operating (initial priming, imprinting, exposure to Wuhan prejudices all subsequent immune response toward Wuhan). The key finding is that ADE may be a grave concern given the COVID vaccines are based on the original Wuhan strain and not current omicron or future variants.

“Antibody dependent enhancement (ADE) of infection is a safety concern for vaccine strategies. In a recent publication, Li et al. (Cell 184 :4203–4219, 2021) have reported that infection-enhancing antibodies directed against the N-terminal domain (NTD) of the SARS-CoV-2 spike protein facilitate virus infection in vitro, but not in vivo. However, this study was performed with the original Wuhan/D614G strain. Since the Covid-19 pandemic is now dominated with Delta variants, we analyzed the interaction of facilitating antibodies with the NTD of these variants. Using molecular modeling approaches, we show that enhancing antibodies have a higher affinity for Delta variants than for Wuhan/D614G NTDs. We show that enhancing antibodies reinforce the binding of the spike trimer to the host cell membrane by clamping the NTD to lipid raft microdomains.

This stabilizing mechanism may facilitate the conformational change that induces the demasking of the receptor binding domain. As the NTD is also targeted by neutralizing antibodies, our data suggest that the balance between neutralizing and facilitating antibodies in vaccinated individuals is in favor of neutralization for the original Wuhan/D614G strain. However, in the case of the Delta variant, neutralizing antibodies have a decreased affinity for the spike protein, whereas facilitating antibodies display a strikingly increased affinity. Thus, ADE may be a concern for people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors). Under these circumstances, second generation vaccines with spike protein formulations lacking structurally-conserved ADE-related epitopes should be considered.”

The issue is to find a way to reduce, remove circulating virus and this infectious pressure due to the virus. By doing this, you will reduce the amount of circulating available virus that the sub-optimal vaccinal antibodies can put pressure on and drive variants. By pressuring yet not eliminating, the ‘fittest’ variants will overcome the pressure and emerge as the dominant variant. It can be a lethal variant too and this is the key, to reduce the infectious pressure so that the selection pressure can be stopped and no new variants emerge.

The issue is that with high levels of virus circulating (omicron), we also are boosting the vaccinal non-neutralizing Abs that bind to the virus but cannot eliminate it but causes increase in infectiousness, and thus the vaccinee is more susceptible to the virus, thus more infection, and thus resulting more infectious pressure etc. A vicious cycle develops.

The pandemic is not disappearing and the vaccine is causing this. Sub-optimal non-neutralizing COVID vaccine antibodies cannot eliminate the virus and is devastating and driving variant after variant and we are approaching driving highly infectious variants that are also virulent. Resistant to any COVID vaccine. We can never tame the pandemic if we cannot reduce the infectious pressure, as such, cut the chain of transmission. We are placing the virus under pressure and we must take the step to reduce the infectious pressure.

High infectious pressure, and high population immune pressure due to non-neutralizing antibodies that bind to the virus's spike. An ADE system is in play where the non-neutralizing Abs are enhancing infection in the vaccinated.