Q&A #22 : about the origin of dominant immune escape SARS-CoV-2 variants

Question:

How could I be so wrong as to pretend that mass vaccination is responsible for immune escape of more infectious SARS-CoV-2 variants? Isn’t it rather the immunosuppressed people who enable the virus to escape the vaccine-induced immune response? This would also explain why the vaccinees are responsible for breeding immune escape variants: SARS-CoV-2 has now become a chronic infection in vaccinees and -like the situation with HIV- chronic infection leads to immune suppression and causes immune evasion of SARS-CoV-2 because the suboptimal immune response can easily be overcome by viral mutants. All of this is the result of antigenic imprinting/sin, which results in enhanced susceptibility of vaccinees and the development of chronic infection.

Answer:

This reasoning is completely wrong. First, it is critical to understand that the enhanced susceptibility of vaccinees to SARS-CoV-2 does not imply chronicity of infection. The enhanced susceptibility to infection directly results from the recall of potentially neutralizing, vaccine-induced antibodies (Abs), which largely fail to neutralize Omicron variants. Diminished neutralizing capacity may enable the host immune system to recognize the enhancing antigenic site on S(pike)-NTD (N-terminal domain) and thereby elicit infection-enhancing Abs. Fantini et al. (https://pubmed.ncbi.nlm.nih.gov/34384810/) have shown, indeed, that diminished neutralizing capacity of anti-S Abs leads to Ab-dependent enhancement of infection. However, there is no evidence that enhancement of infection in vaccinees leads to chronic infection. On the contrary, enhanced viral clearance by cytolytic T cells would even explain why the amount of virus shed by vaccinees is lower than in the unvaccinated (https://www.medrxiv.org/content/10.1101/2022.01.28.22270044v1; https://www.voiceforscienceandsolidarity.org/scientific-blog/c-19-mass-vaccination-triggers-a-chain-reaction-of-new-pandemics-and-epidemics). There can also be no doubt that the infection-enhancing effect results from increasing resistance of SARS-CoV-2 to the vaccine-induced neutralizing Abs and that viral resistance results from natural selection and dominant propagation of SARS-CoV-2 immune escape variants, a phenomenon that can only be explained by mass C-19 vaccination.

If enhanced susceptibility of vaccinees to SARS-CoV-2 would lead to chronic infection and immune suppression, one would not expect that vaccinees continue being protected against severe C-19 disease and, more recently, are even less prone to developing C-19 disease all together.  The combination of enhanced susceptibility of SARS-CoV-2 infection and protection against severe disease in vaccinees can only be explained by immune dysregulation, and not by immune suppression (like in HIV patients) following repetitive re-infection (still followed by viral clearance). Immune dysregulation involves inhibition of trans infection of susceptible alveolar cells by SARS-CoV-2 tethered to dendritic cells as well as accelerated clearance of virus-infected cells and antigen-presenting cells at an early stage of infection or antigen upregulation and presentation on MHC molecules, respectively. Consequently, the immune response to SARS-CoV-2 is anything but immune suppressed. As already mentioned, this explains why (at least for now!) high viral infectiousness and intrinsic virulence of Omicron BA.4 and BA.5 variants can still be kept in check by the host and prevent severe C-19 disease.  

I am therefore not buying the concept that repetitive SARS-CoV-2 infection in C-19 vaccinees leads to immune suppression and that this is why and how antigenic imprinting/sin causes enhanced susceptibility of vaccinees and promotes immune escape. Dominant propagation of immune escape variants is the consequence of mass vaccination and causes immune dysregulation in vaccinees, thereby leading to their enhanced susceptibility to SARS-CoV-2 infection and protection against severe C-19 disease, not the other way around!

In addition, I am not aware of any conclusive evidence showing that immunosuppressed individuals are responsible for the emergence of dominant immune escape variants in the population. Here are three publications dealing with the topic:

https://www.nejm.org/doi/full/10.1056/NEJMsb210475

https://www.nature.com/articles/s41586-021-03291-y

https://journals.asm.org/doi/10.1128/mSphere.00480-21

Alle of these  publications clearly illustrate that in order for immune escape to occur in SARS-CoV-2-infected individuals, the latter should be in a pre-existing immunocompromised state and treated with convalescent plasma or monoclonal Abs. None of this is the case in the overwhelming majority of vaccinees. In addition, there is no evidence that escape mutants that emerge in such immunocompromised patients are transmitted, or that the types of mutations are comparable to those induced in the vaccinees.

It can, therefore, be unambiguously concluded that immune dysregulation[1] in C-19 vaccinees indirectly results from immune escape driven by mass C-19 vaccination, and not the other way around. This clearly implies that there is no rationale whatsoever to suspect immune suppressed individuals, even if unvaccinated, of breeding immune escape variants that expand in prevalence such as to become the dominant circulating lineage in the population.  

[1] Even if immune ‘dysregulation’ were to be considered a form of immune ‘suppression’, the evidence cited in the text would disprove the hypothesis postulated in the opening question.