Demystification: Vaccination — the only solution against the emergence of variants

The English term debunk has become common in recent years and even more so in this period of crisis. This verb means to demystify, refute, discredit. The YouTube platform is full of videos where conspiracy arguments (or at least those deemed to be conspiracy arguments) are deconstructed in order to expose their errors and often ridicule them in the process. It is a form of fact-checking generally carried out by committed citizens (sometimes by professionals) with knowledge in the field concerned. However, there is no reason why debunking cannot be done on the statements of experts or politicians relayed by the mass media, especially during this vaccination campaign. The purpose of this article is to dissect the argument that the non-vaccinated are producers of variants and that vaccination of the population is the only solution to curb the emergence of these variants.

Recently, several media outlets, as well as the WHO, have presented vaccination as the main tool to fight the emergence of variants (including those resistant to vaccines), which are essentially generated by the non-vaccinated, who are characterized as real factories of variants (1) and as the fuel of the epidemic (2). The argument is constructed as follows:

  1. viruses need hosts to survive. During infection, the virus reproduces and is then transmitted from person to person;
  2. SARS-CoV‑2, like all other coronaviruses, undergoes changes (mutations, recombinations) in its genetic code during replication, resulting in the production of viruses (in its progeny) that are different from the parental strain;
  3. In fact, the more individuals there are to infect, the more opportunities the virus will have to generate variants;
  4. Vaccination slows the spread of the virus;
  5. The higher the vaccine coverage, the less opportunity the virus will have to spread and thus generate variants;
  6. Thus, it is necessary to be massively vaccinated.

As with conspiracy theories, there are factual, but incomplete, elements in this premise that lead to an inaccurate conclusion.

The first two points (a and b) are correct: the virus reproduces in a host and forms variants as a result of spontaneous changes in its genetic makeup. However, what the first point fails to mention is the host range of SARS-CoV‑2. Indeed, there are a variety of animals(3) that carry this coronavirus, some of which transmit it to humans, such as mink(4). Thus, while it is true that a larger number of human individuals provides more opportunities for the virus to create variants (point c), this is only a fraction of the variants that are continuously produced.

Vaccination can indeed slow down the spread of the virus (point d), but this argument is again only partially true. First, the effectiveness of current vaccines is decreasing with emerging variants, including the famous delta(5). Secondly, the vaccination coverage that our government would like to achieve is based on thresholds (originally 70%, but now up to 90%).(6)) within countries individual. However, we live on a globalized planet with a high rate of daily interactions between individuals from different countries, which disturbs these theoretical thresholds (they should therefore be extended to the whole world). And finally: it would be illusory to vaccinate all animals (even if the veterinary pharmaceutical companies dream of it). As a result, the importance of immunization coverage (point (e) and the final conclusion, which is to encourage everyone to get vaccinated to prevent the generation of variants (point f), lose their argumentative power entirely. However, a pre-published study (= not yet peer-reviewed for final publication) confirms the decrease in variant diversity in vaccinees (7), confirming the basic premise. What do you think?

The answer lies in the selection pressure. The so-called mRNA or DNA vaccines used in Western countries are monoclonal. As a reminder, the term monoclonal means that the vaccine is based on a single target (as opposed to so-called polyclonal vaccines, which are based on a multitude of targets). As a result, all variants that have a spike protein (the target) similar to that of the vaccines are recognized by the immune system of the vaccinees. On the other hand, variants that have a mutated spike protein that differs from the original strain (used as a model for vaccines) will escape the immune system’s antibodies. Since mutations occur randomly in viruses, they do not only affect the spike protein. Therefore, variants carrying mutations in the spike protein, making them capable of evading vaccine immunity, are only a subgroup of all variants that exist. This is somewhat similar to dog breed selection. If you want a breed of dog with big ears, you will always select the puppies with the biggest ears among the offspring until you obtain, over the generations, a breed with big ears. But the big-eared puppies are never more than a fraction of the litter among the variety of pups.

It is therefore logical that the diversity of variants is lower in vaccinated individuals, as some of the variants are eliminated by their immune system. In biology, the phenomenon of a decrease in diversity following a selection is called bottleneck. Imagine filling a bottle with balls of different sizes with colors associated with their size. Then a funnel is placed on the bottle and the whole thing is turned upside down. Only balls small enough will pass through this funnel. What is recovered is necessarily less varied in color and size than the array of beads in the original bottle. In biology, this translates into a severe reduction of a population that will be followed by a new demographic expansion. The new individuals that spread will initially be less diverse among themselves than the original population, until other biological processes come into play again (selection pressures, etc.). As an analogy, we can imagine a drastic decrease of rabbits on an island. The survivors will then repopulate the whole island, all individuals resembling each other. As time passes, different selection pressures (e.g. predation) will cause the offspring to diversify, giving rise to rabbits of different colors, sizes, etc.

Let’s get back to the point (if we can afford this expression). SARS-CoV‑2 has spread to the world’s population. The bottleneck it is currently experiencing is due to monoclonal vaccines. The diversity of variants will therefore decrease until one (or a few) variants escape vaccine immunity. These variants will then discover a deserted island (the population that has not yet had the covid-19, vaccinated or not) and will spread. As time goes on, new variants will be born, increasing the diversity again. However, a counter-argument can be put forward: after a bottleneck phenomenon, another fate (than demographic expansion) is possible: extinction. This is true and is the outcome that authorities hope for the coronavirus. But it is very likely that the virus will not disappear and that it will become endemic (= permanent in humans), as several researchers think(8). Most importantly, we must not forget that SARS-CoV‑2 is a zoonotic disease and that it can replicate in animals that will also contribute to the production of variants. But is this bottleneck a bad thing?

It is possible that mass vaccination with an imperfect vaccine (= that reduces severe forms, but does not prevent transmission of the virus, as is the case with current vaccines in Western countries (9)) could paradoxically have undesirable consequences. Indeed, vaccinated persons infected with SARS-CoV‑2 will only be able to transmit, by definition, resistant variants that have survived vaccine immunity. These variants will spread to the susceptible population, including the vaccinated population. Rather than vaccinating only the at-risk population, the strategy of vaccinating everyone induces vaccine immunity that is identical in everyone, making them vulnerable to resistant variants. Natural immunity, on the other hand, is unique to each individual and is therefore more effective in stopping the spread of the virus. A pre-published Israeli study suggests that natural immunity is better for the delta variant (10). Remember that natural immunity is polyclonal. In addition, one person’s immune response is not the same as another’s, so a variant that may escape one person’s immunity will be destroyed by another’s immune system. Logistically, a virus circulates more rapidly than a vaccibus, so the acquisition of natural immunity is faster. Paradoxically, by massively vaccinating the population, our societies induce an artificial immunity at the expense of a more robust natural immunity that could lead more rapidly to herd immunity, which is the goal of the vaccination campaign! Add to this the fact that since vaccines have undesirable side effects, the extent and intensity of which are now beginning to be increasingly visible, the ethics of vaccinating a large fraction of the population who would not suffer from covid-19 is, to say the least, questionable.

There is a final risk in the vaccine strategy: the risk of the emergence of a more virulent variant than the previous ones. Human selection by an imperfect vaccine could potentially result in even more dangerous variants. This was particularly the case for Marek’s disease in chickens(11). Generally, viruses naturally tend towards less aggressive variants, because for their propagation, it is more favorable that its hosts remain alive long enough for a maximum of contaminations. This is because the more contagious and benign viruses will be transmitted most quickly, pushing aside those that are more deadly and less contagious. The explanation of the authors of this study with the reverse phenomenon is that using an imperfect vaccine disrupts this natural tendency of viruses to become less virulent. Indeed, the vaccine induces antibodies that immunize against the virus of interest, preventing its spread. In fact, all the variants recognized by these antibodies will be eliminated, except those that have properties that allow them to escape. 

With autumn just around the corner, the weather conditions will soon be favorable for the spread of SARS-CoV‑2 variants. The danger is to see the emergence of variants that are both resistant to vaccines and more virulent.

Therefore, it is quite possible that among the variants blocked by immunity are the more competitive (and less dangerous) ones, and among the resistant ones that bypass immunity (and are transmitted) are more pernicious variants. Applied to SARS-CoV‑2, the risk in Western countries is to have selected vaccine-resistant variants through the powerful vaccination campaign in the middle of the epidemic. The vaccines were administered during a period when coronaviruses are less likely to be transmitted: the summer. However, with fall just around the corner, weather conditions favorable to the spread of SARS-CoV‑2 variants will soon set in. The danger is to see the emergence of variants that are both resistant to vaccines and more virulent.

The example of this study should remind us that the effects of an intense vaccination campaign in the midst of an epidemic can have consequences opposite to those desired. It is therefore appropriate to question the current vaccine campaign, whose reasoning seems to be much more often in the realm of sophistry (= false reasoning that appears to be valid by an author, whose purpose is to deceive) rather than paralogy (= false reasoning that appears to be valid by an author of good faith).

Notes et références
  1. Exemple de quelques médias diffusant le message que les non-vaccinés sont des usines à variants et que la vaccination est le moyen de lutte contre ces variants : (1) La Libre Belgique — « Des usines à variants », « Mais à quoi pensent ces gens ? » : comment les personnes non-vaccinées pourraient contribuer à l’émergence de nouveaux variants: https://www.lalibre.be/planete/sante/2021/07/04/des-usines-a-variants-mais-a-quoi-pensent-ces-gens-comment-les-personnes-non-vaccinees-pourraient-contribuer-a-lemergence-de-nouveaux-variants-QH7C5QOSDFHFJIVYWJHGELG2WY/ (2) La Dernière Heure — « Des usines à variants », « Mais à quoi pensent ces gens ? »: comment les personnes non-vaccinées pourraient contribuer à l’émergence de nouveaux variants: https://www.dhnet.be/actu/sante/des-usines-a-variants-mais-a-quoi-pensent-ces-gens-comment-les-personnes-non-vaccinees-pourraient-contribuer-a-l-emergence-de-nouveaux-variants-60e1ba71d8ad581ce11f3b59 (3) Marianne — Vacciner, seule solution pour limiter l’émergence de nouveaux variants: https://www.marianne.net/societe/sante/vacciner-seule-solution-pour-limiter-lemergence-de-nouveaux-variants (4) Business Insider — Les personnes non vaccinées pourraient devenir une ‘usine à variants’, selon un médecin: https://www.businessinsider.fr/les-personnes-non-vaccinees-pourraient-devenir-une-usine-a-variants-selon-un-medecin-188035 (5) L’Organisation Mondiale de la Santé — Variants du virus et leurs effets sur les vaccins contre la COVID-19:https://www.who.int/fr/news-room/feature-stories/detail/the-effects-of-virus-variants-on-covid-19-vaccines
  2. RTBF — Premier pays à vacciner, Israël est en ce moment celui qui enregistre le plus de contaminations au Covid par habitant au monde : comment l’expliquer ?
  1. Abdel-Moneim AS, Abdelwhab EM. Evidence for SARS-CoV‑2 Infection of Animal Hosts. Pathogens. 2020;9(7):529. Published 2020 Jun 30. doi:10.3390/pathogens9070529 Singla R, Mishra A, Joshi R, Jha S, Sharma AR, Upadhyay S, Sarma P, Prakash A, Medhi B. Human animal interface of SARS-CoV‑2 (COVID-19) transmission: a critical appraisal of scientific evidence. Vet Res Commun. 2020 Nov;44(3–4):119–130. doi: 10.1007/s11259-020–09781‑0. Epub 2020 Sep 14. PMID: 32926266; PMCID: PMC7487339

  1. Oude Munnink BB, Sikkema RS, Nieuwenhuijse DF, Molenaar RJ, Munger E, Molenkamp R, van der Spek A, Tolsma P, Rietveld A, Brouwer M, Bouwmeester-Vincken N, Harders F, Hakze-van der Honing R, Wegdam-Blans MCA, Bouwstra RJ, GeurtsvanKessel C, van der Eijk AA, Velkers FC, Smit LAM, Stegeman A, van der Poel WHM, Koopmans MPG. Transmission of SARS-CoV‑2 on mink farms between humans and mink and back to humans. Science. 2021 Jan 8;371(6525):172–177. doi: 10.1126/science.abe5901. Epub 2020 Nov 10. PMID: 33172935; PMCID: PMC7857398
  1. Centers for Disease Control and Prevention (Etats-Unis) — Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV‑2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance — Eight U.S. Locations, December 2020–August 2021 | MMWR: https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e4.htm Nature — COVID vaccines protect against Delta, but their effectiveness wanes: https://www.nature.com/articles/d41586-021–02261‑8

  1. Ouest France — La vaccination peut-elle empêcher l’apparition de nouveaux variants ?: https://www.ouest-france.fr/sante/virus/coronavirus/la-vaccination-peut-elle-empecher-l-apparition-de-nouveaux-variants-c102d158-e0b2-11eb-9be0-01246e2ebe9b Avis du conseil scientifique français du 6 Juillet 2021: https://solidarites-sante.gouv.fr/IMG/pdf/avis_conseil_scientifique_6_juillet_2021_actualise_8_juillet_2021.pdf
  1. Cet article est une pré-publication: Niesen MJM, Anand P, Silvert E, Suratekar R, Pawlowski C, Ghosh P, Lenehan P, Hughes T, Zemmour D, O’Horo JC, Yao JD, Pritt BS, Norgan A, Hurt RT, Badley AD, Venkatakrishnan AJ and Soundararajan V. COVID-19 vaccines dampen genomic diversity of SARS-CoV‑2: Unvaccinated patients exhibit more antigenic mutational variance. medRxiv 2021.07.01.21259833; doi: https://doi.org/10.1101/2021.07.01.21259833.
  1. Nature — The coronavirus is here to stay — here’s what that means: https://www.nature.com/articles/d41586-021–00396‑2

  1. Idem reference 5
  1. Gazit S, Shlezinger R, Perez G, Lotan R, Peretz A, Ben-Tov A, Cohen D, Muhsen K, Chodick G, Patalon T. Comparing SARS-CoV‑2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections. MedRxiv doi: https://doi.org/10.1101/2021.08.24.21262415 Lire aussi au sujet de l’immunité naturelle les références dans l’article suivant :Block J. Vaccinating people who have has covid-19: why doesn’t natural immunity count? BMJ 2021; 374:n2101 doi. 10.1136/bmj.n2101

  1. Read AF, Baigent SJ, Powers C, et al. Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens. PLoS Biol. 2015;13(7):e1002198. Published 2015 Jul 27. doi:10.1371/journal.pbio.1002198
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