November 12, 2023

First develop your knowledge before even dreaming of developing new Covid-19 vaccines

First develop your knowledge before even dreaming of developing new Covid-19 vaccines

I read the following contribution from Milton Simba Kambarami: While warning about the ongoing immune escape, this person doesn't seem to realize that the spread of more infectious immune escape variants directly results from mass vaccination, which, since Omicron, has led to immune refocusing. Otherwise, they would not propose investing more money and resources into developing new Covid-19 (c-19) vaccines.

Which epitopes on spike protein that the circulating SARS-CoV-2 lineages have not yet developed resistance against should a new vaccine target? How can one even make a proposal about new vaccines without understanding the underlying dynamics of the evolving interactions between the host and the immune system? I strongly recommend this individual to subscribe to my course to learn that:

  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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Geert Vanden Bossche received his DVM from the University of Ghent, Belgium, and his PhD degree in Virology from the University of Hohenheim, Germany. He held adjunct faculty appointments at universities in Belgium and Germany. After his career in Academia, Geert joined several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay Biologicals) to serve various roles in vaccine R&D as well as in late vaccine development.

Geert then moved on to join the Bill & Melinda Gates Foundation’s Global Health Discovery team in Seattle (USA) as Senior Program Officer; he then worked with the Global Alliance for Vaccines and Immunization (GAVI) in Geneva as Senior Ebola Program Manager. At GAVI he tracked efforts to develop an Ebola vaccine. He also represented GAVI in fora with other partners, including WHO, to review progress on the fight against Ebola and to build plans for global pandemic preparedness.

Back in 2015, Geert scrutinized and questioned the safety of the Ebola vaccine that was used in ring vaccination trials conducted by WHO in Guinea. His critical scientific analysis and report on the data published by WHO in the Lancet in 2015 was sent to all international health and regulatory authorities involved in the Ebola vaccination program. After working for GAVI, Geert joined the German Center for Infection Research in Cologne as Head of the Vaccine Development Office. He is at present primarily serving as a Biotech / Vaccine consultant while also conducting his own research on Natural Killer cell-based vaccines.


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