Pseudovirus neutralization assays provide convenient hocus-pocus to dazzle the public
The Innate Neutralizing Antibodies Providing Protection are REAL but Are Quickly Eroded by Spike Protein Exposures (Vaccines and More Frequent Infections in the Highly Vaccinated)
In this article Dr. Vanden Bossche rightly questions the validity of pan- neutralizing antibodies to S protein demonstrated against all variants:
Dr. Marian Laderoute offers this explanation:
Neutralization across the board? say what?
A quick look at the Wang Q et al bioRxiv pre-paper (Nov 27, 2023) reveals the authors used a pseudovirus assay with preparation of the variant particles in the human 293 T cells and then used Vero-E6 cells as the indicator cells. The magic of this neutralizing assay is that the pseudovirus particles now bear human HERV-K102 envelope derived from creation of the particles in human cells (but not when pseudoparticles are produced in non-human cells) to which INNATE antibodies in the blood of the immunized individuals to HERV-K102 envelope will in fact neutralize [see evidence for these antibodies in C19 patients here: Apostolou E, et al. Front Immunol. 2022 Oct 20;13:949787. doi: 10.3389/fimmu.2022.949787].
These antibodies disappear at 6 months or so (sooner if mRNA spike shots or infections are more frequent and if there are comorbidities) which exacerbates the loss of innate immunity, and so it is said "one must get boosted every 6 months".
While the first booster shot (the famous mRNA third shot) converts dangerous IgG1/IgG3 to tolerogenic IgG4 apparently this doesn't happen in the upper respiratory tract (URT).
[NOTE: the unvaccinated generally don’t have IgG1 and IgG3 to spike in the URT which is why the highly vaccinated are at higher increased risks of SARS-CoV-2 infections over the unvaccinated [1,2]. Remember the Cleveland Clinic data?
1. Guerrieri M, Francavilla B, Fiorelli D, et al. Nasal and salivary mucosal humoral immune response elicited by mRNA BNT162b2 COVID-19 vaccine compared to SARS-CoV-2 natural infection. Vaccines (Basel). 2021 Dec 18;9(12):1499. doi: 10.3390/vaccines9121499.
2. Aksyuk AA, Bansal H, Wilkins D, et al. AZD1222-induced nasal antibody responses are shaped by prior SARS-CoV-2 infection and correlate with virologic outcomes in breakthrough infection. Cell Rep Med. 2022 Dec 15:100882. doi: 10.1016/j.xcrm.2022.100882.
So the highly vaxed person remains at high risk of URT infection due to ADE in the URT but generally without LRT infection (unless it is some other pathogen) because systematically the harmful IgG1/3 are converted to not harmful IgG4. {This generates increased infectivity in the URT by ADE.}
But the repeated infections compromises trained (innate) immunity of macrophages AND INDUCES IMMUNOSENESCENCE OF MACROPHAGES via the released spike protein, so now the host is at higher risk of non-COVID morbidity and mortality.
This includes heart issues, cardiovascular issues, tumors, turbo-cancers, autoimmune diseases, neurodegenerative diseases and so on [see Laderoute M, Discovery Medicine, 2015, 2020].
However, IN THEORY at some point the variant spike may be so different (caused by repeated vaccination of the population) that the body will once again produce IgG1/3 to the virus, and there will not be sufficient innate immunity to defend the host (because the spike exposures eroded trained immunity in the meantime).
Possibly, optimal vitamin D3 will still protect against severe COVID-19 and death if this catastrophe happens. Ivermectin (antiviral that blocks/prevents immunosenescence of macrophages) and/or methylprednisolone (which might induce HERV-K102 particle production trained immunity while downmodulating adaptive immunity) would be expected to strongly help those with co-morbidities and at higher risk of severe COVID-19 (multi-vaccinated especially with the mRNA shots).
The unvaccinated will be affected less as they have not had their trained immunity eroded and immunosenescence of macrophages exacerbated like the multiply vaccinated.
So SURPRISINGLY, it may be possible to generate more virulent variants if one keeps vaccinating into the pandemic.
These concepts are similar to what I think Geert proposes and may be useful as an alternative/similar explanation.
For more info on ADE and trained innate immunity please see
Laderoute, M. Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness. Preprints 2023, 2023120185. https://doi.org/10.20944/preprints202312.0185
Do you correspond with the authors and editors of these papers?
It would be so useful to read the referees' comments as well to see if any of them have a clue.
Regards as always.
Thank you again, Dr. Marian. And I do appreciate your use of capital letters and bold font. Helpful to the non-scientist.