After a year of pandemic management that has caused a lot of ink to flow, the long awaited and announced vaccine is finally here. Note that the term « vaccine » was used more in the singular than in the plural, which is reminiscent of the deus ex machina of Greek tragedies: a divine intervention that suddenly unravels a desperate situation. The defenders of technology (under the banner of progressivism) are obviously welcoming the arrival of the miracle solution that would put an end to the epidemic that is shaking the planet. Any deviation from this framework of thought elicits the use of propagandist-sounding vocabulary: « conspiracy », « covidiot » or « reassurance » (the latter being particularly violent in my opinion, because it implies that the Thesimple fact of reassuring one’s entourage is already ethically questionable; since when is it deplorable to simply reassure people in psychological distress?)

The pharmaceutical industry, as a whole, offers us four types of vaccines against SARS-CoV‑2.

Two are based on « classic » technologies that have been in use for nearly a century and consist of:

1) Attenuated viruses (e.g. from companies: Sinopharm, Sinovac), polyclonal vaccine (i.e. targeting several components of SARS-CoV‑2)

2) virus fragments (e.g. companies: Novavax), monoclonal vaccine (targeting only one component of the virus).

The other two are built with new « gene » technologies and are composed of:

3) viral genetic material in the form of RNA, never before applied to humans (e.g. companies: Pfizer/BioNTech, Moderna), monoclonal vaccine.

4) a viral vector that delivers viral genetic material (RNA) of interest (in this case, that of SARS-CoV‑2) (e.g. companies: AstraZeneca/Oxford, Johnson & Johnson), monoclonal vaccine.

All these vaccines are not equal and to reject them all without considering them separately would be as narrow-minded as considering the COVID-19 vaccination as a deus ex machina to our pandemic (or rather deus ex vaccina). Although they are based on different technologies, these vaccines have some commonalities. Their development has been extremely rapid, considering that the development of a new vaccine can take years (sometimes more than 10 years, according to the WHO)(1). Indeed, when developing new vaccines, part of the time is lost in waiting for various authorizations, regulations and funding and another part is devoted to the development of the vaccine technology. In the case of SARS-CoV‑2, these two phases could be shortened because on the one hand the usual administrative delays were accelerated and on the other hand the studies on these new technologies had already started before the arrival of the pandemic. But making vaccines in a hurry is never ideal, especially when it comes to evaluating their effectiveness and the extent of side effects of new technologies. This is especially true for this virus, which has specific characteristics that make the design of a vaccine complicated.

Two main fears: the effectiveness and side effects of vaccines

I. Efficiency

Vaccine efficacy depends not only on the biotechnology, but on the nature of the target: the virus itself. One of the reasons why there are no long-lasting vaccines against viruses that cause colds or flu is that these viruses evolve rapidly. This is typically the case for RNA viruses (of which coronaviruses are one). In addition to mutations (i.e. transformation of the genetic code by « error »), they also frequently recombine (which is the equivalent of genetic « exchanges » between viruses)(2). If the coronaviruses are able to accomplish « ping-pong between animal species (including the human) »(3), it is well thanks to this faculty of transformation.

A monoclonal vaccine (i.e., one that targets only one component of the virus) will most likely be short-lived and limited in time by the appearance of any SARS-CoV‑2 variant. On the other hand, a polyclonal vaccine offers the possibility for vaccinees to develop defenses against different parts of the virus, thus reducing the risk of the virus escaping (after evolution) from herd immunity.

In the case of the SARS-CoV‑2 monoclonal vaccines, the targeted component is the « spike » protein (the famous button-shaped surface proteins that are represented on the surface of the virus when it is drawn). The strategic choice of this target is based on its immune stimulating nature. This protein is used by the virus to recognize its host and is prone to mutations, several of which have already been documented(4). Thus, the hope of eradicating this virus overlooks the following possibilities:

  • the spike protein of the virus mutates and the vaccine becomes ineffective. The new variant is as dangerous as the previous one, if not worse;
  • Darwinian selection pressure favors spike-independent transmission of the virus (a less common, but documented mechanism(5));
  • the virus recombines with another virus and changes in such a way as to escape the vaccine (a scenario that is all the more dangerous if it is another epidemic coronavirus, such as MERS-CoV(6));
  • the virus disappears from the human host (ideal scenario) and « takes refuge » in animal reservoirs, where it continues to evolve. The return of a variant that escaped the vaccine could thus not be excluded. It should be noted that it is impossible to eradicate a zoonosis (i.e. an infection shared between humans and other animals) unless all the host animals are vaccinated or eliminated.

The pharmaceutical industry is obviously proposing a solution: that of renewing the vaccines and providing the doses according to a vaccination strategy that consists of administering a SARS-CoV‑2 vaccine several times a year. For a price of 20 euros per dose, twice a year for a market targeting a large part of the world’s population, this is indeed very interesting for the industry and for stock market investment funds. It is a market strengthened by political decision of 300 to 500 billion euros per year with negotiated financial guarantees (among others with the European Union(7)).

II. Side effects

Concerns about side effects and tolerance to modern (RNA) vaccines against COVID-19 are frequently dismissed by resolute techno-progressives, who refer to clinical trials. While admitting that a clinical trial (such as Pfizer’s) of 38,000 people is promising and that it would be difficult to demand more from a company, it is extremely unlikely that the results could be as encouraging when applied to larger numbers of several orders of magnitude. While the figure of 38,000 may seem high, it can never encompass a diversity of health profiles equivalent to the population for which the vaccine is intended. The epidemic being planetary and the percentage necessary for the acquisition of a collective immunity being situated between, approximately, 60–70% according to the WHO(8)This would give a theoretical target of about five billion people, or a population a million times more than in the Pfizer trial (assuming that the number of Theactual number of people vaccinated is likely to be lower). According to Pfizer data(9), 0.6% of vaccinated subjects experienced « serious adverse events » (compared to 0.5% in the placebo group). But 0.1% of life-threatening side effects on a billion person scale would put a million lives at risk! Any preventive measure must do less harm than the pathology in question. However, the lethality of SARS-CoV‑2 (around 0.2%(10)) is far from being comparable to that of plague or Ebola epidemics. Is it justifiable to risk all these serious adverse events?

Since the RNA vaccine technology is new, it is imperative to validate it. Conventional vaccines can be certified very quickly, as their technologies are known and therefore do not pose any problems (this is why two flu vaccines can be produced and certified per year). For RNA vaccines, certification without applying the same basic rigor would be incorrect. Note that those who claim to be committed to the precautionary principle with barrier gestures and masks are suddenly absent from the debate!

To the list of concerns already mentioned can also be added:

  • the ineffectiveness of such new viral vector vaccines in people who would have natural immunity to the vector itself (the vector is an « empty » human virus, filled with RNA coding for SARS-CoV‑2 antigens). This is a benign, real problem, but one that no one seems to care about (a problem that does not exist with conventional vaccines)
  • A possible recombination of the vector/SRAS-CoV‑2 construct with natural virus(es). This is a much more serious problem. In the scientific community (and this is getting a bit technical, but may be of interest to some readers with expertise in the field), there are two arguments against this concern (i) gene exchanges only occur between viruses of the same type (between DNA viruses on the one hand and RNA viruses on the other, but not between these two categories) and (ii) any catastrophic event would be unlikely. The first argument is correct, but examples of exchanges between RNA and DNA viruses exist and cannot be ignored(11). The second dialectic, which consists in brushing aside fears under the pretext that even if risks exist, they are so improbable that they can be dismissed, demonstrates the insouciance of techno-progressives in the face of calculations of probabilities. Just imagine, for example, that only one hundredth of the world’s population would be vaccinated in the end, and that twice a year. This would still represent hundreds of millions of doses per year, integrating into thousands/millions of our cells several viral particles carrying the vaccine, all potentially capable of transforming… The adverse event that could give rise to a nanoscopic Frankenstein’s monster would have to be less than one chance in hundreds of billions.
  • Let’s add to this probability an additional, more basic, but absolutely crucial condition: the fact that one cannot administer a vaccine when one is actively infected. For example, when injecting flu vaccines, the physician must ensure that the patient does not carry the virus. This would open the door wide to wild recombinations. Have governments considered in their vaccination strategies to screen people for SARS-CoV‑2 (including asymptomatic ones) before administering the vaccine?

Note that those who claim to be committed to the precautionary principle with barrier gestures and masks are suddenly absent from the debate!

For these reasons, in 2016 « the Brighton Collaboration » (a global non-profit vaccine safety network for healthcare professionals) formulated guidelines following the recommendations of the U.S. Food and Drug Administration FDA and the European Medicines Agency) for vector vaccine design. These recommendations include (i) review of knowledge related to viral recombination, (ii) the extent of the timeliness of such events, (iii) examining the mechanisms leading to these events, and (iv) the implementation of safeguards as well as methods for detecting these adverse events(12). Have these principles been respected?

We are told that the advantage of modern vaccines, compared to the classical ones, is their ability to be modulated to adapt to a changing situation. Thus, if a particularly virulent variant were to suddenly spread, modern vaccines would have an advantage. If this is indeed correct, these new vaccines that over-stimulate and modulate immunity have nevertheless a major disadvantage compared to more classical vaccines: that of interfering with the immune balance itself. The principle of these gene vaccines is to force our own cells to produce viral fragments (rather than injecting them) against which the body will become immune. When it is our cells that produce foreign particles, the risk of an autoimmune reaction that spills over into anaphylactic shock or rejection of our own cells is higher. In practice, we do not know what will happen in a whole category of patients, starting with those suffering from immune or endocrinological pathologies (we are thinking here, for example, of Alzheimer’s patients, type I diabetics, rheumatic and articular diseases, Cushing’s or Addison’s diseases, certain thyroid pathologies, etc.) This represents a significant fraction of the population and deserves to be investigated.

There is one final concern about the science behind all these vaccines (of all types): that of vaccine strategy. Belgium has decided to give priority to vaccinating at-risk individuals, including the elderly, and healthcare workers. While the strategy makes sense for the latter category of people, it makes less sense for the elderly. The virus is only dangerous for certain people with weak immune systems. However, the principle of vaccination is to stimulate the immune system and therefore, the vaccine will never be more effective than the immune system on which it relies… In America, it is the children who are vaccinated against the seasonal flu, because even if this category of the population does not suffer from the disease caused by these viruses, they can transmit it. However, it responds well to the vaccine and through herd immunity it protects those who do not respond well. Establishing a vaccination strategy based on fragile people who are also the most exposed to autoimmune risks seems to be less effective and therefore seems to me to be more a political communication decision than a scientific one.

As for other reasons why I should view these vaccines with caution, Paul Lannoye clearly describes in his article his critical examination of the implementation of these vaccines and their links to the EU in « About the Vaccine. Neither conspiracy nor blind belief »(13). I also invite readers to consult the report by Dr. Vélot (molecular geneticist at the University of Paris-Saclay and President of the Scientific Council of CRRIGEN)(14)A summary of this report is also provided by Valérie Tilman in « Covid-19: Expert report on vaccines using GMO technologies: summary of Dr Vélot’s note ».(15). This analysis, independent of mine, comes to the same conclusions. It is also worth noting that the first data from the vaccination campaign are starting to become available and are consistent with our concerns. The latter did not confirm the efficacy of the Pfizer/BioNTech vaccine three weeks after the first dose, prompting a review of the schedule for the second dose in several countries(16).

My training in environmental virology has allowed me to study the extremely dynamic nature of viruses and their reproductive cycles. They represent the most abundant biological entity on Earth and reproduce with a formidable speed and multiplicity. They are capable of killing us as well as saving us. So, to protect my family and loved ones, it is obvious to me that we all need to be vaccinated with the standard vaccines. But as always, you have to know the difference between what is effective and safe and what is less so. Honest communication and a standards-based approach are required. It is curious that not only was this communication not made, but that by forcing vaccines as the only solution — while vaccines are never curative therapies — the authorities have forgotten that medicine is first and foremost about treating people… What is happening with the practice of general practitioners, the first line of defense? We can’t examine patients and measure the severity of their condition through online consultation and requests for COVID tests alone…Where are we with curative therapies?

Kaarle P., PhD in Environmental Virology

Notes et références
  2. Quelques articles scientifiques au sujet de la recombinaison chez les virus à ARN et les coronavirus :Sanjuán R, Domingo-Calap P. Mechanisms of viral mutation. Cell Mol Life Sci. 2016 Dec;73(23):4433–4448. doi: 10.1007/s00018-016‑2299‑6. Epub 2016 Jul 8. PMID: 27392606; PMCID: PMC5075021.Worobey M, Holmes EC. Evolutionary aspects of recombination in RNA viruses. J Gen Virol. 1999 Oct;80 ( Pt 10):2535–2543. doi: 10.1099/0022–1317-80–10-2535. PMID: 10573145.Kumar N, Sharma S, Barua S, Tripathi BN, Rouse BT. Virological and Immunological Outcomes of Coinfections. Clin Microbiol Rev. 2018 Jul 5;31(4):e00111-17. doi: 10.1128/CMR.00111–17. PMID: 29976554; PMCID: PMC6148187.Banner LR, Lai MM. Random nature of coronavirus RNA recombination in the absence of selection pressure. Virology. 1991 Nov;185(1):441–5. doi: 10.1016/0042–6822(91)90795‑d. PMID: 1656597; PMCID: PMC7131166.
  3. et
  4.–02544‑6 etLi Q, Wu J, Nie J, Zhang L, Hao H, Liu S, Zhao C, Zhang Q, Liu H, Nie L, Qin H, Wang M, Lu Q, Li X, Sun Q, Liu J, Zhang L, Li X, Huang W, Wang Y. The Impact of Mutations in SARS-CoV‑2 Spike on Viral Infectivity and Antigenicity. Cell. 2020 Sep 3;182(5):1284–1294.e9. doi: 10.1016/j.cell.2020.07.012. Epub 2020 Jul 17. PMID: 32730807; PMCID: PMC7366990.Et 
  5. Graham RL, Baric RS. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J Virol. 2010 Apr;84(7):3134–46. doi: 10.1128/JVI.01394–09. Epub 2009 Nov 11. PMID: 19906932; PMCID: PMC2838128.
  6. Baddal B, Cakir N. Co-infection of MERS-CoV and SARS-CoV‑2 in the same host: A silent threat. J Infect Public Health. 2020 Sep;13(9):1251–1252. doi: 10.1016/j.jiph.2020.06.017. Epub 2020 Jun 22. PMID: 32622797; PMCID: PMC7306724 et Banerjee A, Doxey AC, Tremblay BJ, Mansfield MJ, Subudhi S, Hirota JA, Miller MS, McArthur AG, Mubareka S, Mossman K. Predicting the recombination potential of severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. J Gen Virol. 2020 Dec;101(12):1251–1260. doi: 10.1099/jgv.0.001491. Epub 2020 Sep 9. PMID: 32902372.
  8.‑5/episode‑1 dans‑a-detail/herd-immunity-lockdowns-and-covid-19
  9. Pfizer-BioNTech COVID-19 vaccine (BNT162, PF-0730208) vaccines and related biological products advisory committee briefing document. Pour les données citées : Table 8, p. 46
  10. Ioannidis, J.P.A. « Infection fatality rate of COVID-19 inferred from seroprevalence data » Bulletin of the World Health Organization. Article ID : BLT.20.265892;
  11. Stedman KM. Deep Recombination: RNA and ssDNA Virus Genes in DNA Virus and Host Genomes. Annu Rev Virol. 2015 Nov;2(1):203–17. doi: 10.1146/annurev-virology-100114–055127. Epub 2015 Sep 2. PMID: 26958913.
  12. Condit RC, Williamson AL, Sheets R, Seligman SJ, Monath TP, Excler JL, Gurwith M, Bok K, Robertson JS, Kim D, Michael Hendry R, Singh V, Mac LM, Chen RT; Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG). Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains. Vaccine. 2016 Dec 12;34(51):6610–6616. doi: 10.1016/j.vaccine.2016.04.060. Epub 2016 Jun 23. PMID: 27346303; PMCID: PMC5204448.

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