The fight against the Covid-19 pandemic mobilizes private (laboratories, foundations, pharmaceutical manufacturers, protective equipment, …) and public (governments, universities, WHO, hospitals, …) actors. Most of them have engaged in a cooperation to find a vaccine against Covid-19.
The search for vaccines against Covid19 is based on several past experiences: the research started during the SARS epidemics in 2002-2003 or the MERS in 2012 (Middle East Respiratory Syndrome), the improvement of the efficacy of already existing vaccines against other coronaviruses (feline, canine, porcine) or other viruses (influenza, BCG, …). However, regardless of the progress of its research, none of its research has yet definitively validated the testing phase in humans. Currently, the search for a vaccine involves about 35 companies and universities that have already launched more than 300 clinical studies. These studies have made it possible to start developing more than 150 vaccines, including 8 in phase 3 (https://www.infovac.ch/fr/les-vaccins/par-maladie/coronavirus-covid-19).
The future vaccine against Covid-19 is built from 4 possibilities: either by using recombinant protein from a virus cell, or by using a ribonucleic acid (RNA) close to the DNA of the virus, or by modifying the genetic material of the virus (vector vaccine), or by inactivating the virus before injecting it.
Prior to being marketed, the vaccine must undergo four development phases before receiving authorization: the pre-clinical phase (study of the molecule, its effects on cells and on animal behavior), phase 1 (evaluating tolerance and adverse effects in human volunteers), phase 2 (defining the optimal dose of the drug and its effects on fewer than 500 patients) and phase 3 (comparing the efficacy of the future treatment to a placebo or other reference treatment on several thousand people).
The quantities of vaccines to be produced are such that only large groups have the capacity to find production capacity. Sanofi, for example, estimates that it will take at least six months to produce, package and deliver the vaccine to the populations concerned if all these phases are carried out according to the initial schedule and do not fail at each of the test phases. (https://www.lesechos.fr/idees-debats/sciences-prospective/coronavirus-la-fabrication-et-la-distribution-des-vaccins-en-5-questions-1206147).
The 8 vaccine projects in phase 3 are :
CanSino Biologics (China) based on a vector vaccine. Numerous side effects have appeared and efficacy seems limited ("Initial results of this coronavirus vaccine are mixed"),
Sinopharm (China) on an inactivated virus basis
Moderna (USA) based on an RNA vaccine. Greater side effects than with other vaccines have occurred (https://www.lesechos.fr/industrie-services/pharmacie-sante/coronavirus-ou-en-sont-les-laboratoires-dans-la-course-au-vaccin-1223739).
Pfizer and BioNTech (Germany) on the basis of an RNA-based vaccine,
AstraZeneca (Great Britain), based on a vector-based vaccine, has organized its production line to offer vaccines by the end of 2020 (https://www.usinenouvelle.com/article/astrazeneca-fournira-a-l-europe-400-millions-de-doses-de-son-futur-vaccin-contre-le-covid-19.N975331).
Sinovac Biotech (China) on the basis of an inactivated virus
Janssen /Johnson&Johnson (Belgium) on the basis of a vector-based vaccine (https://www.rtbf.be/info/dossier/epidemie-de-coronavirus/detail_janssen-pharmaceutica-lance-officiellement-les-essais-cliniques-d-un-vaccin-contre-le-coronavirus?id=10550205)
Russia is developing a vector-based vaccine, but lack of transparency on phases makes it impossible to prove efficacy against the virus (https://www.sudouest.fr/2020/09/11/voici-ce-que-nous-apprennent-les-resultats-des-essais-du-vaccin-russe-contre-le-coronavirus-7835039-7498.php).
Approximately 15 other vaccine projects are in phase 2, including :
Sanofi/GSK on the basis of a recombinant protein influenza vaccine (https://www.lemonde.fr/planete/article/2020/09/03/sanofi-et-gsk-commencent-les-tests-sur-l-homme-pour-leur-candidat-vaccin-contre-le-covid-19_6050833_3244.html)
Inovio Pharmaceuticals is studying a DNA-based vaccine and plans trials in the fall of 2020 (https://www.sciencesetavenir.fr/sante/usa-resultats-preliminaires-positifs-pour-un-autre-vaccin-experimental-contre-le-covid-19_145608)
Novavax Inc. based on a recombinant protein vaccine (https://www.mypharma-editions.com/novavax-et-takeda-collaborent-sur-un-candidat-vaccin-contre-la-covid-19-au-japon)
CureVac based on an RNA vaccine, and partnered with Tesla to reduce vaccine production costs (https://www.industriepharma.fr/covid-19-tesla-va-fabriquer-les-imprimantes-a-arnm-pour-le-vaccin-de-curevac,111746).
Further research is under development:
The German Infection Research Center is adapting the research conducted on MERS to propose a vaccine against Covid-19 (https://www.lequotidiendumedecin.fr/actus-medicales/recherche-science/lessai-sur-un-vaccin-contre-le-mers-ouvre-la-voie-un-vaccin-contre-le-sars-cov-2).
In Israel, the Ministry of Defense's Biological Research Institute announced a Phase 3 trial in October (Gantz: Trials of Israel's COVID-19 vaccine will begin in mid-October) and Tel Aviv University is studying a vaccine that can teach the immune system to block the virus as it enters the body (https://www.ami-universite-telaviv.com/index.php/2013-05-26-08-41-51/recherche/sciences/medecine/1204-un-vaccin-contre-le-coronavirus-d%C3%A9velopp%C3%A9-%C3%A0-l%E2%80%99universit%C3%A9-de-tel-aviv-brevet%C3%A9-aux-etats-unis).
In Canada, the International Vaccine Centre plans to begin human trials in the fall of 2020 (https://ici.radio-canada.ca/nouvelle/1706057/furets-humains-maladie-sante-recherche-essais-clinique-vido-intervac-saskatchewan).
Institut Pasteur and other laboratories are working to improve the BCG vaccine, https://www.pourquoidocteur.fr/Articles/Question-d-actu/33193-Covid-19-vaccin-le-BCG-pourrait-proteger-virus.
Among all these projects, especially the 8 in phase 3, and considering the steps taken previously, the 4 that seem to be the most successful are :
The vaccine developed by AstraZeneca even though the tests were momentarily stopped due to the appearance of a serious side effect in one subject. The tests were able to resume in Great Britain (https://www.numerama.com/sciences/646830-coronavirus-pourquoi-les-essais-du-vaccin-dastrazeneca-sont-mis-en-pause.html).
The vaccine developed by Sinovac, although no results from phases 1 and 2 have yet been published (https://www.lindependant.fr/2020/08/23/covid-19-un-vaccin-chinois-developperait-des-anticorps-chez-97-des-personnes-en-un-mois-et-pour-2-ans-9031443.php).
The vaccine developed by Moderna has demonstrated non-toxicity and antibody production in phases 1 and 2 (https://www.wedemain.fr/Vaccins-et-traitements-contre-la-Covid-19-les-dernieres-avancees_a4614.html).
The vaccine developed by Pfizer (with BioNTech) allows the development of a high level of neutralizing antibodies. (https://www.industriepharma.fr/covid-19-resultats-positifs-pour-le-vaccin-de-pfizer-et-biontech,111721)
These two vaccines are the only ones to have an active Phase 3 trial in the U.S. (pending U.S. approval) and to have published clinical trial protocols for transparency. Phase 3 results are expected in October or November and would allow the vaccine to be available in early 2021. (https://www.lefigaro.fr/flash-eco/covid-19-deux-fabricants-americains-de-vaccins-devoilent-les-regles-de-leurs-essais-cliniques-20200917)
However, the discovery of one or more vaccines will not mean the end of the pandemic, as the vaccine may only be effective in some people. Hence the parallel use of existing treatments (including the use of plasma from cured patients). Drugs that have already proven effective in similar situations include: dexamethasone, anakinra, chloroquine, azithromycin, EIDD-2801 (already effective in MERS and SARS), remdesivir (used for Ebola), ivermectin, avigan or tocilizumab (https://www.linternaute.com/actualite/guide-vie-quotidienne/2484525-vaccin-et-medicaments-contre-le-covid-ca-avance-ou-ca-recule-le-point-sur-les-etudes).
All of these treatments, already proven or in the testing phase, confirm that the objective is not to eradicate the virus, but to learn to live with it as with the seasonal flu virus and to limit its serious effects as much as possible, since the responses may vary from one age group to another or according to the immune fragility of the patients.
Conversely, the solution advocating community immunity means that a significant percentage of the population must be immunized for the virus to stop circulating (67% for France, for example). Since herd immunity is generally reached after 2 or 3 epidemic waves, the cost calculated to reach this level would result in a minimum of 100,000 deaths in France ("COVID-19, herd immunity: where are we?" published in Nature Reviews Immunology).
Once the vaccine(s) is/are licensed, the issue of production is crucial in order to be able to offer the number of doses sufficient to vaccinate the world population. A minimum of 2 doses per person and more is generally accepted for fragile populations. Bill Gates estimates the need for a minimum of 7 billion doses to cover about 70% of the population. (https://www.futura-sciences.com/sante/breves/coronavirus-selon-bill-gates-il-faudra-moins-deux-doses-vaccin-personne-coronavirus-2950/). The Bill and Melinda Gates Foundation is already very active in projects to improve health care around the world and is also involved in projects supported by the WHO. For example, in the fight against Covid-19, the Gates Foundation has provided financial support to SK Bioscience of Korea to develop and produce a vaccine. (https://pulsenews.co.kr/view.php?year=2020&no=765380).
Bill Gates is regularly criticized for his commitment to health in particular, as when a speech given at a TED conference in 2015 on the lessons to be learned from Ebola warning that "if something kills more than 10 million people on Earth in the coming decades, it is more likely to be a contagious virus, rather than a war" is taken up in conspiracy theories and identifies him as a creator of Covid-19. In this speech, Bill Gates reported on the knowledge and causes of high mortality in the world, just as an American intelligence agency was able to alert as early as 2005 on the risks of a deadly virus coming from China in view of the knowledge of the terrain it had at that time (https://www.challenges.fr/entreprise/défense/ces-rapports-qui-anticipait-la-crise-du-coronavirus 703306).
While the search for a vaccine against Covid-19 is now in the hands of the pharmaceutical laboratories, the fight for prevention and against the spread of the virus remains a strong remit of the WHO, which gives recommendations to fight the virus, coordinates and assists in prevention and treatment by standing alongside governments. However, doubts have arisen among some leaders, particularly in the West, about the impartiality and reliability of the recommendations given by the WHO. These doubts come first and foremost from the WHO's mode of operation, which sets standards and communicates them without having any power to impose the actions it recommends and only intervenes according to the situations reported to it: it does not question its sources, so when China reports that the virus is not being communicated to humans, the WHO communicates this information as it stands. These operating biases have been compounded by a bias linked to the person of Director General Tedros Adhanom Ghebreyesus, who succeeded the Chinese Margaret Chan in this position, and Ethiopian, a country heavily dependent on Chinese investment (https://www.europe1.fr/international/chine-et-crise-du-covid-19-l'who-maybe-under-influenced-who-pays-most (https://www.europe1.fr/international/chine-et-crise-du-covid-19-l'oms-maybe-under-influenced-who-pays-most (https://www.europe1.fr/international/chine-et-crise-du-covid-19-l'oms-maybe-under-influenced-who-pays-most (https://www.europe1.fr/international/chine-et-crise-du-covid-19-l'oms-maybe-under-influenced-who-pays-most)).
These characteristics may explain why the WHO, despite reports from Taiwanese and Chinese doctors in Wuhan, continued to relay official Chinese claims of non-transmission of Covid-19 to humans until the end of January 2020. Some countries have followed its recommendations, such as France, for example, which did not commit itself to taking strict measures before the change in the WHO's position. China's geopolitical weight and diplomatic correctness within the WHO also help to understand the decisions of the WHO in January 2020 to advise against general travel or trade restrictions as these restrictions mainly impact China. And after the recognition by China on its soil of the dangerousness of the virus and the entry into force of very strict measures, the Director General of the WHO could only welcome the measures taken and translate them into international recommendations. These initial positions and the lack of self-criticism on the start of crisis management continue to overshadow the current work of WHO. (https://www.institutmontaigne.org/blog/loms-la-pandemie-et-linfluence-chinoise-un-premier-bilan). The more time passes, the more it appears that China has deliberately delayed providing information on the virus to WHO, which considered the information relayed to it by Chinese officials to be accurate and safe. (https://www.france24.com/fr/20200602-coronavirus-une-enqu%C3%AAte-accuse-la-chine-d-avoir-tard%C3%A9-%C3%A0-livrer-des-informations-%C3%A0-l-oms)
Will Covid-19 evolve like SARS in 2003? Nothing is less sure. For SARS, the first patient appeared in China in November 2002 and informed the WHO in February 2003. Respiratory masks are required for public travel in the main cities concerned. In July 2003, the epidemic was contained with some resurgence until 2004. A person infected with SARS usually presents symptoms within 3 days, but can last up to 10 days.s Strict isolation, control and protection measures have limited the progression of the virus. Gradually, all people infected with SARS were isolated and the virus slowly died out on its own.
In 2003, the words of Professor Jean-Claude Manuguerra, virologist at the Pasteur Institute, which were echoed by the Swiss medical journal, alerted to the Chinese concealment since the first cases appeared at the end of 2002 and the authorities chose to hide the phenomenon at a time when it would have been possible to contain it. This led to an ascending epidemic phase, which was difficult to control, and he anticipated that as SARS spread in the population, it would find ways to improve its mode of transmission, making the respiratory disease increasingly contagious. This same mechanism was replicated 17 years later with Covid-19.(https://www.revmed.ch/RMS/2003/RMS-2436/1060)
In October 2007, an article in Clinical Microbiology Reviews stated that the SARS case-fatality rate was 10%. In addition, the large reservoir of coronavirus-containing animals and the practice of eating exotic mammals in southern China is a proven risk of contracting new coronaviruses. It is all the more recommended to develop a culture of anticipation to face these new challenges. (https://cmr.asm.org/content/cmr/20/4/660.full.pdf)
For Covid-19, the origin is the one identified in 2003 (an exotic mammal), and if the virus is less lethal, it spreads on a larger scale and especially infected persons may show no external symptoms, be asymptomatic, or develop symptoms up to 2 weeks after being contaminated. These characteristics explain why the virus circulates more and longer, unless we maintain a quarantine for everyone as long as the virus circulates (https://the conversation.com/the-mystery-disappearance-of-the-first-virus-free-and-why-we-will-need-a-vaccinator-for-us-disposal-of-the-second-virus-137957).
The common factor in the spread of the 2 viruses is the lack of transparency of the Chinese authorities, the delays taken to communicate the existence of the pandemic in China and the will to minimize, at first, the seriousness of the situation. (https://www.franceinter.fr/monde/au-fait-comment-s-est-terminee-l-epidemie-de-sras-en-2003)
Once these pitfalls have been overcome, for SARS as for Covid-19, individual protection measures, isolation, generalization of tests allow to reduce the spread of the virus until its disappearance in the case of SARS or the discovery of vaccines and effective palliative treatments, while waiting for the possible disappearance of the virus, in the case of Covid-19.
Louis Tourronde
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