Geert Vanden Bossche, DMV, PhD, independent virologist and vaccine expert, formerly employed at GAVI and The Bill & Melinda Gates Foundaton.

To all authorites, scientsts and experts around the world, to whom this concerns: the entre world populaton.

I am all but an antvaxxer. As a scientst I do not usually appeal to any platorm of this kind to make a stand on vaccine-related topics. As a dedicated virologist and vaccine expert I only make an excepton when health authorites allow vaccines to be administered in ways that threaten public health, most certainly when scientfc evidence is being ignored. The present extremely critcal situaton forces me to spread this emergency call. As the unprecedented extent of human interventon in the Covid-19- pandemic is now at risk of resultng in a global catastrophe without equal, this call cannot sound loudly and strongly enough.

As stated, I am not against vaccinaton. On the contrary, I can assure you that each of the current vaccines have been designed, developed and manufactured by brilliant and competent scientsts. However, this type of prophylactc vaccines are completely inappropriate, and even highly dangerous, when used in mass vaccinaton campaigns during a viral pandemic. Vaccinologists, scientsts and clinicians are blinded by the positve short-term efects in individual patents, but don’t seem to bother about the disastrous consequences for global health. Unless I am scientfcally proven wrong, it is difcult to understand how current human interventons will prevent circulatng variants from turning into a wild monster.

Racing against the clock, I am completng my scientfc manuscript, the publicaton of which is, unfortunately, likely to come too late given the ever increasing threat from rapidly spreading, highly infectous variants. This is why I decided to already post a summary of my fndings as well as my keynote speech at the recent Vaccine Summit in Ohio on LinkedIn. Last Monday, I provided internatonal health organizatons, including the WHO, with my analysis of the current pandemic as based on scientfcally informed insights in the immune biology of Covid-19. Given the level of emergency, I urged them to consider my concerns and to initate a debate on the detrimental consequences of further ‘viral immune escape’. For those who are no experts in this feld, I am ataching below a more accessible and comprehensible version of the science behind this insidious phenomenon.

While there is no tme to spare, I have not received any feedback thus far. Experts and politcians have remained silent while obviously stll eager to talk about relaxing infecton preventon rules and ‘springtme freedom’. My statements are based on nothing else but science. They shall only be contradicted by science. While one can barely make any incorrect scientfc statements without being critcized by peers, it seems like the elite of scientsts who are currently advising our world leaders prefer to stay silent. Sufcient scientfc evidence has been brought to the table. Unfortunately, it remains untouched by those who have the power to act. How long can one ignore the problem when there is at present massive evidence that viral immune escape is now threatening humanity? We can hardly say we didn’t know – or were not warned.

In this agonizing leter I put all of my reputaton and credibility at stake. I expect from you, guardians of mankind, at least the same. It is of utmost urgency. Do open the debate. By all means: turn the tde!

Author: Geert Vanden Bossche, DVM, PhD (March 6, 2021) – https://www.linkedin.com/in/geertvandenbossche/

PUBLIC HEALTH EMERGENCY OF INTERNATIONAL CONCERN

Why mass vaccinaton amidst a pandemic creates an irrepressible monster

THE key queston is: why does nobody seem to bother about viral immune escape? Let me try to explain this by means of a more easily understood phenomenon: Antmicrobial resistance. One can easily extrapolate this scourge to resistance to our self-made ‘antviral antbiotcs’. Indeed, antbodies (Abs) produced by our own immune system can be considered self-made antviral antbiotcs, regardless of whether they are part of our innate immune system (so-called ‘natural’ Abs’) or elicited in response to specifc pathogens (resultng in so-called ‘acquired’ Abs). Natural Abs are not germ-specifc whereas acquired Abs are specifcally directed at the invading pathogen. At birth, our innate immune system is ‘unexperienced’ but well-established. It protects us from a multtude of pathogens, thereby preventng these pathogens from causing disease. As the innate immune system cannot remember the pathogens it encountered (innate immunity has no so-called ‘immunological memory’), we can only contnue to rely on it provided we keep it ‘trained’ well enough. Training is achieved by regular exposure to a myriad of environmental agents, including pathogens. However, as we age, we will increasingly face situatons where our innate immunity (ofen called ‘the frst line of immune defense’) is not strong enough to halt the pathogen at the portal of entry (mostly mucosal barriers like respiratory or intestnal epithelia). When this happens, the immune system has to rely on more specialized efectors of our immune system (i.e., antgen-specifc Abs and T cells) to fght the pathogen. So, as we grow up, we increasingly mount pathogen-specifc immunity, including highly specifc Abs. As those have stronger afnity for the pathogen (e.g., virus) and can reach high concentratons, they can quite easily outcompete our natural Abs for binding to the pathogen/virus. It is precisely this type of highly specifc, high afnity Abs that current Covid-19 vaccines are inducing. Of course, the noble purpose of these Abs is to protect us against Covid-19. So, why then should there be a major concern using these vaccines to fght Covid-19?

Well, similar to the rules applying to classical antmicrobial antbiotcs, it is paramount that our self-made ‘antviral antbiotcs’ are made available in sufcient concentraton and are tailored at the specifc features of our enemy. This is why in case of bacterial disease it is critcal to not only chose the right type of antbiotc (based on the results from an antbiogram) but to also take the antbiotc for long enough (according to the prescripton). Failure to comply with these requirements is at risk of grantng microbes a chance to survive and hence, may cause the disease to fare up. A very similar mechanism may also apply to viruses, especially to viruses that can easily and rapidly mutate (which is, for example, the case with Coronaviruses); when the pressure exerted by the army’s (read: populaton’s) immune defense starts to threaten viral replicaton and transmission, the virus will take on another coat so that it can no longer be easily recognized and, therefore, atacked by the host immune system. The virus is now able to escape immunity (so-called: ‘immune escape’). However, the virus can only rely on this strategy provided it stll has room enough to replicate. Viruses, in contrast to the majority of bacteria, must rely on living host cells to replicate. This is why the occurrence of ‘escape mutants’ isn’t too worrisome as long as the likelihood for these variants to rapidly fnd another host is quite remote. However, that’s not partcularly the case during a viral pandemic! During a pandemic, the virus is spreading all over the globe with many subjects shedding and transmitng the virus (even including asymptomatc ‘carriers’). The higher the viral load, the higher the likelihood for the virus to bump into subjects who haven’t been infected yet or who were infected but didn’t develop symptoms. Unless they are sufciently protected by their innate immune defense (through natural Abs), they will catch Covid-19 disease as they cannot rely on other, i.e., acquired Abs. It has been extensively reported, indeed, that the increase in S (spike)-specifc Abs in

Author: Geert Vanden Bossche, DVM, PhD (March 6, 2021) – https://www.linkedin.com/in/geertvandenbossche/

asymptomatcally infected people is rather limited and only short-lived. Furthermore, these Abs have not achieved full maturity. The combinaton of viral infecton on a background of suboptmal Ab maturity and concentraton enables the virus to select mutatons allowing it to escape the immune pressure. The selecton of those mutatons preferably occurs in the S protein as this is the viral protein that is responsible for viral infectousness. As the selected mutatons endow the virus with increased infectous capacity, it now becomes much easier for the virus to cause severe disease in infected subjects. The more people develop symptomatc disease, the beter the virus can secure its propagaton and perpetuaton (people who get severe disease will shed more virus and for a longer period of tme than asymptomatcally infected subjects do). Unfortunately enough, the short-lived rise in S-specifc Abs does, however, sufce to bypass people’s innate/natural Ab. Those are put out of business as their afnity for S is lower than the afnity of S-specifc Abs. This is to say that with an increasing rate of infecton in the populaton, the number of subjects who get infected while experiencing a momentary increase in S- specifc Abs will steadily increase. Consequently, the number of subjects who get infected while experiencing a momentary decrease in their innate immunity will increase. As a result, a steadily increasing number of subjects will become more susceptble to getng severe disease instead of showing only mild symptoms (i.e., limited to the upper respiratory tract) or no symptoms at all. During a pandemic, especially youngsters will be afected by this evoluton as their natural Abs are not yet largely suppressed by a panoply of ‘acquired’, antgen-specifc Abs. Natural Abs, and natural immunity in general, play a critcal role in protectng us from pathogens as they consttute our frst line of immune defense. In contrast to acquired immunity, innate immune responses protect against a large spectrum of pathogens (so don’t compromise or sacrifce your innate immune defense!). Because natural Abs and innate immune cells recognize a diversifed spectrum of foreign (i.e., non-self) agents (only some of which have pathogenic potental), it’s important, indeed, to keep it sufciently exposed to environmental challenges. By keeping the innate immune system (which, unfortunately, has no memory!) TRAINED, we can much more easily resist germs which have real pathogenic potental. It has, for example, been reported and scientfcally proven that exposure to other, quite harmless Coronaviruses causing a ‘common cold ’ can provide protecton, although short-lived, against Covid-19 and its loyal henchmen (i.e., the more infectous variants).

Suppression of innate immunity, especially in the younger age groups, can, therefore, become very problematc. There can be no doubt that lack of exposure due to stringent containment measures implemented as of the beginning of the pandemic has not been benefcial to keeping people’s innate immune system well trained. As if this was not already heavily compromising innate immune defense in this populaton segment, there comes yet another force into play that will dramatcally enhance morbidity and mortality rates in the younger age groups: MASS VACCINATION of the ELDERLY. The more extensively the later age group will be vaccinated and hence, protected, the more the virus is forced to contnue causing disease in younger age groups. This is only going to be possible provided it escapes to the S-specifc Abs that are momentarily raised in previously asymptomatcally infected subjects. If the virus manages to do so, it can beneft from the (momentarily) suppressed innate immunity, thereby causing disease in an increasing number of these subjects and ensuring its own propagaton. Selectng targeted mutatons in the S protein is, therefore, the way to go in order for the virus to enhance its infectousness in candidates that are prone to getng the disease because of a transient weakness of their innate immune defense.

But in the meantme, we’re also facing a huge problem in vaccinated people as they’re now more and more confronted with infectous variants displaying a type of S protein that is increasingly diferent from

Author: Geert Vanden Bossche, DVM, PhD (March 6, 2021) – https://www.linkedin.com/in/geertvandenbossche/

the S editon comprised within the vaccine (the later editon originates from the original, much less infectous strain at the beginning of the pandemic). The more variants become infectous (i.e., as a result of blocking access of the virus to the vaccinated segment of the populaton), the less vaccinal Abs will protect. Already now, lack of protecton is leading to viral shedding and transmission in vaccine recipients who are exposed to these more infectous strains (which, by the way, increasingly dominate the feld). This is how we are currently turning vaccinees into asymptomatc carriers shedding infectous variants.

At some point, in a likely very near future, it’s going to become more proftable (in term of ‘return on selecton investment’) for the virus to just add another few mutatons (maybe just one or two) to the S protein of viral variants (already endowed with multple mutatons enhancing infectousness) in an atempt to further strengthen its binding to the receptor (ACE-2) expressed on the surface of permissive epithelial cells. This will now allow the new variant to outcompete vaccinal Abs for binding to the ACE receptor. This is to say that at this stage, it would only take very few additonal targeted mutatons within the viral receptor-binding domain to fully resist S-specifc ant-Covid-19 Abs, regardless whether the later are elicited by the vaccine or by natural infecton. At that stage, the virus will, indeed, have managed to gain access to a huge reservoir of subjects who have now become highly susceptble to disease as their S-specifc Abs have now become useless in terms of protecton but stll manage to provide for long-lived suppression of their innate immunity (i.e., natural infecton, and especially vaccinaton, elicit relatvely long-lived specifc Ab tters). The susceptble reservoir comprises both, vaccinated people and those who’re lef with sufcient S-specifc Abs due to previous Covid-19 disease). So, MISSION ACCOMPLISHED for Covid-19 but a DISASTROUS SITUATION for all vaccinated subjects and Covid-19 seropositve people as they’ve now lost both, their acquired and innate immune defense against Covid-19 (while highly infectous strains are circulatng!). That’s ‘one small step for the virus, one giant catastrophe for mankind’, which is to say that we’ll have whipped up the virus in the younger populaton up to a level that it now takes litle efort for Covid-19 to transform into a highly infectous virus that completely ignores both the innate arm of our immune system as well as the adaptve/acquired one (regardless of whether the acquired Abs resulted from vaccinaton or natural infecton). The efort for the virus is now becoming even more negligible given that many vaccine recipients are now exposed to highly infectous viral variants while having received only a single shot of the vaccine. Hence, they are endowed with Abs that have not yet acquired optmal functonality. There is no need to explain that this is just going to further enhance immune escape. Basically, we’ll very soon be confronted with a super-infectous virus that completely resists our most precious defense mechanism: The human immune system.

From all of the above, it’s becoming increasingly difcult to imagine how the consequences of the extensive and erroneous human interventon in this pandemic are not going to wipe out large parts of our human populaton. One could only think of very few other strategies to achieve the same level of efciency in turning a relatvely harmless virus into a bioweapon of mass destructon.

It’s certainly also worth mentoning that mutatons in the S protein (i.e., exactly the same protein that is subject to selecton of escape mutatons) are known to enable Coronaviruses to cross species barriers. This is to say that the risk that vaccine-mediated immune escape could allow the virus to jump to other animal species, especially industrial livestock (e.g., pig and poultry farms), is not negligible. These species are already known to host several diferent Coronaviruses and are usually housed in farms with high stocking density. Similar to the situaton with infuenza virus, these species could than serve as an

Author: Geert Vanden Bossche, DVM, PhD (March 6, 2021) – https://www.linkedin.com/in/geertvandenbossche/

additonal reservoir for SARS-COVID-2 virus.

As pathogens have co-evolved with the host immune system, natural pandemics of acute self-limitng viral infectons have been shaped such as to take a toll on human lives that is not higher than strictly required. Due to human interventon, the course of this pandemic has been thoroughly disturbed as of the very beginning. Widespread and stringent infecton preventon measures combined with mass vaccinaton campaigns using inadequate vaccines will undoubtedly lead to a situaton where the pandemic is getng increasingly ‘out of control’.

Paradoxically, the only interventon that could ofer a perspectve to end this pandemic (other than to let it run its disastrous course) is …VACCINATION. Of course, the type of vaccines to be used would be completely diferent from conventonal vaccines in that they’re not inducing the usual suspects, i.e., B and T cells, but NK cells. There is, indeed, compelling scientfc evidence that these cells play a key role in facilitatng complete eliminaton of Covid-19 at an early stage of infecton in asymptomatcally infected subjects. NK cells are part of the cellular arm of our innate immune system and, alike natural Abs, they are capable of recognizing and atacking a broad and diversifed spectrum of pathogenic agents. There is a sound scientfc ratonale to assume that it is possible to ‘prime’ NK cells in ways for them to recognize and kill Coronaviruses at large (include all their variants) at an early stage of infecton. NK cells have increasingly been described to be endowed with the capacity to acquire immunological memory. By educatng these cells in ways that enable them to durably recognize and target Coronavirus-infected cells, our immune system could be perfectly armed for a targeted atack to the universe of Coronaviruses prior to exposure. As NK cell-based immune defense provides sterilizing immunity and allows for broad- spectrum and fast protecton, it is reasonable to assume that harnessing our innate immune cells is going to be the only type of human interventon lef to halt the dangerous spread of highly infectous Covid-19 variants.

If we, human beings, are commited to perpetuatng our species, we have no choice lef but to eradicate these highly infectous viral variants. This will, indeed, require large vaccinaton campaigns. However, NK cell-based vaccines will primarily enable our natural immunity to be beter prepared (memory!) and to induce herd immunity (which is exactly the opposite of what current Covid-19 vaccines do as those increasingly turn vaccine recipients into asymptomatc carriers who are shedding virus). So, there is not one second lef for gears to be switched and to replace the current killer vaccines by life-saving vaccines.

I am appealing to the WHO and all stakeholders involved, no mater their convicton, to immediately declare such acton as THE SINGLE MOST IMPORTANT PUBLIC HEALTH EMERGENCY OF INTERNATIONAL CONCERN.

Author: Geert Vanden Bossche, DVM, PhD (March 6, 2021) – https://www.linkedin.com/in/geertvandenbossche/