Immediate cancellation of all ongoing Covid-19 mass vaccination campaigns should now become THE most acute health emergency of international concern.
Executive summary (see also slide appended on p.6 below) The manuscript, which is in now in the process of being finalized, should shed some light on how the virus and especially its interaction with the host immune system determines the natural course (i.e., without human intervention) of a Coronavirus (CoV) pandemic. The interplay between host immune defense and viral immune escape determines the course of a natural CoV pandemic (including a natural Covid-19 pandemic).
In the clinic, viral immune escape is known to occur when the neutralizing capacity of serum antibodies (Abs) does not suffice to fully eliminate highly mutable viruses (e.g., CoV) for lack of their concentration or affinity. In a CoV pandemic setting, seroconversion occurs against a background of high infectious pressure and is, therefore, prone to promote viral immune escape.
The first wave of disease1 (and mortality) primarily affects elderly people (or otherwise immunocompromised subjects). Selective (i.e., adaptive) immune escape is expected to cause this wave to transition into a more severe, second wave in younger age groups. Subsequently, non-selective (i.e., innate) as well as selective immune escape operated by increasingly infectious viral variants will trigger a third wave. The latter would primarily affect subjects who recovered from disease they contracted during the first wave as their seroneutralising Abs do no longer properly match the new circulating viral variants. This third wave of disease (and mortality) would come to an end when those who recovered from the disease will have mounted new functional Abs against these immune escape variants. As seroconversion in this population will now occur much faster (due to recall of cross-reactive T helper memory cells) and as the majority of the young and middle-aged population will either be seronegative or have seroconverted already by the time the third wave starts to expand, chances are slim for the virus to escape the host’s Ab response. Asymptomatic2, seronegative individuals (i.e., the vast majority of young and middle-aged people) may spread virus upon (re-)infection and hence, constitute a relevant source of viral transmission. However, CoV infection in these asymptomatic carriers is abrogated after a short period of viral shedding. Viral clearance in these subjects is likely to occur through activation of NK cells. The latter are capable of recognizing CoV-associated, antigen (Ag)-nonspecific patterns on the surface of CoV-infected epithelial target cells. As killing by NK cells is, therefore, not Ag-specific and as seroconversion
NOTE1 For the purpose of the manuscript, ‘disease’ refers to severe Covid-19 disease with involvement of lower respiratory airways
NOTE 2 For the purpose of the manuscript, ‘asymptomatic’ infection refers to CoV infection which does not cause clinically relevant symptoms or only causes a mild level of disease (i.e., only involving upper respiratory airways) –Page 1.
in asymptomatically infected subjects is only short-lived, viral immune escape does not normally occur. Consequently, new, more infectious, variants are unlikely to emerge from this population as long as viral infectiousness does not dramatically increase.
At the point of ‘no immune escape’, the pandemic will be under control and merge into an endemic infection. However, as long as the point of ‘no immune escape’ isn’t reached, any additional immune selection pressure, for example as a result of suboptimal concentration or affinity of Ag-specific (e.g., spike protein-specific) Abs, will allow the virus to rapidly unfold more infectious, immune escape variants. Additional immune selection pressure, especially when exerted during the second wave of a CoV pandemic, is likely to precipitate and amplify viral immune escape. This might even cause the second and third wave to merge into a single huge wave of mortality and disease that affects all layers of the population (possibly, with the exception of small children).
Especially mass vaccination campaigns, particularly when conducted in the midst of a pandemic, are prone to exerting enormous immune pressure on circulating virus strains. This is because the vaccine is used in an increasingly infectious context (as escape variants are more infectious). Mass vaccination campaigns will accelerate the emergence of even more infectious immune escape variants. This because the number of vaccine recipients who seroconvert within a given time period will dramatically increase 3 . In addition, Ag-specific, high affinity Abs induced by any of the current vaccines will outcompete natural, broadly protective mucosal IgM antibodies as the latter only bind with low affinity to the receptor-binding domain of CoV (RBD). This will particularly affect natural resistance of younger age groups which - thanks to a well-trained innate immune system- resisted disease during the first wave. The new circulating CoV variants may now even be able to escape the host’s CoV variant-nonspecific line of immune defense at the mucosal portal of entry. These age groups may, therefore, become more susceptible to symptomatic infection and shedding caused by more infectious variants.
But mass vaccination campaigns will also have severe consequences for those who got vaccinated first (mostly the elderly or people with underlying disease or those who are otherwise immunocompromised). In the highly likely event that mass vaccination will soon result in antiviral resistance (see below), these people will have no single bit of immunity left to rely upon. In contrast to the infectious circulating virus, current vaccines do either not contain any critical killer cell motif or fail to activate dedicated killer cells. It goes, therefore, without saying that vaccine-induced immune responses will inevitably result in a dramatic enhancement of morbidity and mortality rates in all of the human population (except for small children?). Note 3: Alike naturally infected subjects, vaccine recipients need time to mount a full-fledged Ag-specific Ab response – Page 2.
Further to all of the above, low exposure to circulating CoV strains (e.g., due to stringent containment measures) will increasingly weaken innate mucosal immunity for lack of training. Again, this is particularly relevant for those who - thanks to their sufficient and adequate innate immune defense – got away with asymptomatic infection during the first wave. Stringent and widespread infection prevention measures are now increasingly compromising their innate immunity and rendering them more susceptible to symptomatic infection. Especially the younger age groups may, therefore, end up with relatively higher morbidity and mortality rates, even regardless of the emergence of more infectious viral variants. This is to say that broadly implemented infection prevention measures will only amplify the already detrimental consequences of ongoing mass vaccination campaigns. It is reasonable to assume that the combination of non-selective and selective immune escape will cause morbidity and mortality rates in younger age groups to explode (see figure attached on p.6 below).
The more Covid-19 vaccination campaigns in the young and middle-age groups will be delayed (i.e., relative to their initiation in the elderly), the more they will enhance morbidity and mortality rates in this group: By the time mass vaccination campaigns are about to start in the young and middle-aged groups, a substantial number of these people will already have been infected with Covid-19. Enhanced rates of infection by highly infectiousness viral variants have now significantly increased the likelihood for them to become re-infected while being in the process of seroconverting. So, by the time vaccinations will be initiated, viral immune escape in this group may already be fueling a vicious circle of enhanced viral infectiousness resulting in more seroconversion and hence, more immune escape. Mass vaccination campaigns in this group will only dramatically deteriorate the situation as they will lead to a fast and massive increase in the number of asymptomatic subjects that are in the process of seroconverting against a highly infectious background and, therefore, are prone to promoting viral immune escape. As there is naturally no reason for them to isolate, there will be plenty of opportunity for the highly infectious circulating strains to replicate in the presence of suboptimal Ab titers and, therefore, to escape the host’s immune control.
Hence, the more vaccination campaigns in this group get delayed, the more selection of even more infectious viral variants will be expedited. The ensuing exponential increase in viral immune escape rates will ultimately enable viral variants to even break through vaccine-mediated protection in the vaccinated elderly. As their Abs increasingly mismatch the ever more infectious emerging variants, they will no longer manage to control viral replication and shedding and rapidly allow for massive viral immune escape. Because seroprotective Abs primarily confer protection through targeting Covid-19’s RBD, the virus will now increasingly select mutations in this particular part of the spike protein as those most readily enable the virus to escape vaccine-induced Abs. This will inevitably precipitate resistance to the vaccine. As –Page 3, a result of mass vaccination, people who got the vaccine first will suddenly no longer be protected and, despite vaccination, fall prey to a wave of catastrophic morbidity and mortality.
There can, therefore, be no doubt that current vaccination strategies are rendering the impact of mass vaccination campaigns even more catastrophic and only adding to the magnitude of a pending global health disaster. However, mass vaccination also harms individual health as vaccine-induced variant-specific Abs will outcompete natural variant-nonspecific mucosal Abs for binding to CoV variants and thereby deprive individuals from their broadly protective natural (life)line of immune defense.
As large scale vaccination campaigns combined with the sustained implementation of several containment measures will only expedite the occurrence of viral escape mutations, the illusory hope that current Covid-19 vaccines could generate herd immunity should once and for all be thrown overboard. Along the same line of reasoning, it is not unthinkable that Covid-19 will, once again, cross species barriers. One can definitely not rule out that with growing immunemediated selection of virus variants, Covid-19 is ultimately going to be able to jump to other animal species, especially industrial livestock (e.g., intensive pig and poultry farms with high stocking density) as i) these species are already known to host several different Coronaviruses and ii) variability/ mutations in the very same spike protein, and particularly in the RBD, are known to be responsible for shifts in host tropism/ susceptibility. Similar to the situation with influenza virus, these animal species could then constitute a reservoir for SARS-COVID-2 virus. Depending on the prevalence of circulating animal CoVs in those farms (and hence, the level of trained immunity), those animals could now serve as asymptomatic carriers, thereby constituting a serious threat to humans.
Conclusion: The combination of mass vaccination and infection prevention measures is a recipe for a global health disaster. Following the science, one has to conclude that all age groups (possibly with the exception of small children) will be heavily affected and subject to rates of morbidity and mortality that raise much faster and much higher than those expected to occur during the natural course of a CoV pandemic. This will particularly apply if the sequence of mass vaccinations following the first infectious wave parallels that of natural infection (i.e., immunocompromised people and elderly first, followed by the younger age groups).
No one, for that matter, should be granted a right to implement large-scale pharmaceutic and non-pharmaceutic immune interventions, especially not during a viral pandemic, and certainly not without an in-depth understanding of the immune pathogenesis of a viral pandemic. When one follows the science, and nothing but the science, it becomes extremely difficult to not label –Page 4, ongoing mass vaccination campaigns as a crime, not only to public health but also to individual health.
To substantiate the reasoning above, the manuscript will first explain how components of the innate immune system can protect against Covid-19 and render infections asymptomatic. It will then go on to explain in more detail why and how, in an immunologically Covid-19-naïve population, selective (i.e., adaptive) immune escape shifts the first wave of disease and death from the elderly (and immunocompromised) subjects to those who at the outset of the pandemic got away with asymptomatic infection (i.e., the younger and middle-aged population segment). Similarly, it will be explained how accelerated viral immune escape in the asymptomatically infected population finally shifts back the burst of morbidity and mortality to the elderly, and how the population eventually controls the pandemic by controlling viral immune escape. This will already illustrate the critical importance of desiccating the changing contribution of innate and adaptive immunity to the population’s overall immune defense against a viral pandemic. Understanding these dynamics helps to comprehend the sophisticated course of a natural CoV pandemic, how it eventually merges into an endemic infection and why human intervention has a highly detrimental impact on the refined interplay between the virus and its host. In regard of the latter, the devastating global health impact of ongoing mass vaccination campaigns and accompanying stringent and widespread containment measures will be explained in more detail as the global and individual health consequences could simply be unbearable for many years to come.
After the introductory section on innate immune defense mechanisms relevant to Covid-19, other relevant topics will be addressed in form of questions and answers. Last, a section will be dedicated to the scientific rationale for using NK cell-based vaccines that could provide sterilizing immunity and hence, wipe out Covid-19 and related variants all together. –Page 5.
Author: G. Vanden Bossche, DVM, PhD; 26 February 2021.
The natural course of a CoV pandemic is controlled by the population’s innate and adaptive immunity and dramatically aggravated by antibody-based vaccines when used in mass vaccination campaigns conducted in the course of the pandemic and flanked by stringent containment measures.
NAC: (vaccine resistance ) Natural asymptomatic carrier : for the purpose of this manuscript, NAC is defined as a subject disposing upon a level of innate immunity high enough to resist disease.
nonNAC: For the purpose of this manuscript, nonNAC is defined as a subject who is not endowed with a level of innate immunity high enough to be able to resist disease when exposed to infectious virus during the first wave. –Page 6.
New CoV strain →innate immune escape →{symptomatic infection in nonNACs: 1st wave}→{ [RESERVOIR] asymptomatic infection in NACs: 1st wave } → plus innate immune escape due to MASS CONTAINMENT, → plus adaptive immune escape due to MASS VACCINATION →{ symptomatic infection in NACs: 2nd wave} → plus adaptive immune escape due to vaccine resistance (from MASS VACCINATION)→ { symptomatic infection in nonNACs: 3rd wave} →{ Endemic infection with seasonal flare-ups ( triggered by crowding or lack of exposure to reservoir) }
