We are today witnessing a race for a vaccine. It is a display of strength by the superpowers, led by China, the USA and Great Britain. And while there are indications that the vaccine will be available relatively soon, it may not be available to everyone and may not live up to all the expectations. While there is a need for the vaccine to be produced rapidly, the safe production of vaccines is in everyone’s interest. What is at stake is the confidence not only in this particular vaccine or the general idea of vaccination but all of science.
The pandemic, which has been going on for months, is gradually destroying the social belief in the omnipotence of man. It has also undermined our faith in science, strictly in medicine, which, in the public mind, was supposed to quickly eliminate the virus, or at least immunize us against it. More and more time has passed since the ‚official’ outbreak of the new plague, announced on 11 March 2020 by the World Health Organization (WHO). Meanwhile, there is still no publicly available vaccine, despite the international race maintained by the most recognized laboratories.
How is a vaccine made?
A vaccine is a medicinal product that contains an antigen or antigens that trigger a specific response by the immune system. Thanks to them, the body in contact with an active virus knows how to react and defends itself faster by triggering an immune reaction in the body.
So what is the difficulty in creating a vaccine, if we already have a virus that can undergo one of the already established methods of production? Unfortunately, the less known the pathogen is, the more difficult the whole process is.
This is also the case of the new coronavirus, whose mechanism of action and health symptoms are still not well researched. Therefore, it is difficult to determine what the exact effects of using the vaccine are to be, and what immune effect will be sufficient to prevent the infection and development of the COVID-19 disease.
All the more so, as new, unexpected symptoms of the new coronavirus continue to appear, not only in the respiratory system but also in the nervous system (the neurological consequences of COVID-19 were described in July by scientists in The Lancet). Therefore, the development of a new vaccine is not only technically very difficult and costly but is also subject to very strict rigours for safety reasons. Usually, the entire process takes up to 10 years.
According to the Polish National Institute of Public Health – National Institute of Hygiene, the process of developing new vaccines can be summarized as follows:
- Laboratory tests
- Preclinical tests on animal models (1-1.5 years)
- Phase I clinical trials (1-2 years)
- Phase II clinical trials (2 years or more)
- Phase III clinical trials (3-4 years)
- Preparation of infrastructure for vaccine production (factories, production lines) (approx. 3 years)
- Marketing authorization process (minimum 210 days)
Such a long time of preclinical and clinical trials and registration allows limiting the postponed negative effects of the medicinal product, which will not be seen in a short observation period. Like all other medicines, vaccines are controlled for safety as long as they are on the market and the list of side effects is always open.
A great acceleration
Meanwhile, in the case of the SARS-CoV-2 virus vaccine, the entire process has already been significantly accelerated. The unfortunate metaphor used by the US Department of Health might have suggested some procedures were actually being bypassed, which, of course, is not the case. Operation Warp Speed (spacecraft speed in the science-fiction series Star Trek, which bends space-time) aims to deliver 300 million doses of „a safe, effective vaccine against COVID-19 by January 2021”. That is extremely fast taking into account our experience so far.
A similar position was taken in early July by Soumya Swaminathan, chief scientist of the World Health Organization, recognizing that regulators will accelerate approval of a new vaccine, and the process of testing the safety and effectiveness of the product can be accelerated to 6 months instead of years.
AstraZeneca, working on the most promising vaccine in the world, AZD1222, together with scientists from Oxford, has announced that it is already starting the production of the finished substance. If they obtain the appropriate approval, the product will be immediately ready for sale.
This information, apart from fuelling the fears of a growing number of anti-vaccine groups, is also bothering the scientific world, requiring even more careful observation of the safety and effectiveness profile of the hastily prepared product. The durability of the immune effect is also questionable. Since billions of doses are required, the process of producing and administering the vaccine will take up to several years. Will this be enough to contain pandemics, or will new outbreaks continue to erupt in areas where vaccination will lose its validity? Finally, how will vaccine effectiveness be determined? After all, even the White House advisor, Anthony Fauci, has stated that even only 70% efficiency would be satisfactory. But is it really enough?
The accelerated process may be defended by the argument that known and proven methods of vaccine production are used (although this is not entirely true because the technology based on information RNA adopted by Moderna and Pfizer has never been used in any approved vaccine). Despite these concerns, the WHO is trying to reassure world public opinion. Katherine O’Brien, head of the organisation’s vaccination department, believes that the rapid rollout of a new vaccine does not compromise safety or effectiveness.
It should also not be forgotten that we operate in a state of war, which requires special costs and efforts. This is done with the enormous credit of trust that societies around the world have placed in scientists. And this was in the midst of the crisis of trust in the preventive medical actions of the state that affected the world even before the epidemic.
If widespread vaccination is found not to be effective or safe enough, the whole intricate structure of modern preventive medicine can collapse. However, if the new vaccine is both effective and safe, and it ends the global crisis, we all benefit. What is at stake is not only the vaccination of the population but also the restoration of faith in medicine. Therefore, the record-breaking preparation time should not be the main criterion for its success. Although it is certainly extremely important to maintaining global health.
Current race status
As of July 24, 2020, 166 vaccines are under development. Of these, 8 are in Phase I (testing safety), another 12 are in Phase II (extended safety and immunity testing), and 5 are in Phase III (subject to extensive testing for efficacy in a large and diverse population).
The AZD1222 vaccine developed by the University of Oxford and the AstraZeneca company is currently at the forefront of the race to create the first publicly available vaccine.
It is based on a weakened adenovirus that originally caused a cold in chimpanzees. The adenovirus was genetically altered, which stopped it from replicating any longer. Genes encoding the spike proteins used by the coronavirus to infect human cells have also been added. The principle of the vaccine is therefore relatively simple – it is to teach the body to recognize the spikes characteristic of SARS-CoV-2, so that when the infection happens, the immune system will know how to act.
The results of Phase I and II clinical trials published in The Lancet showed that the vaccine is not only safe but induces an immune response leading to the production of antibodies and T lymphocyte stimulation. The study was conducted on 1077 patients aged 18-55 years. In all of them, the drug caused the expected reaction. However, it is still not known how strong the immune system’s response must be for protection against the coronavirus to be effective. This question should be answered by the third phase of the clinical trial, which will cover 5,000 volunteers from Brazil, 10,500 in Great Britain and 30,000 in the USA.
The second on the list of the most promising vaccines is PiCoVacc – created by the Chinese Sinovac Biotech and the Brazilian Butantan Institute, based on inactivated coronavirus. The vaccine has already undergone phases I and II and has proven to be not only effective but also safe in mice, rats and rhesus monkeys. Unfortunately, its results in humans have still not been published, although the researchers said in the press that 90% of the 734 volunteers experienced an immune reaction. A phase III clinical trial that started in Brazil is currently underway and will involve 8,870 participants.
Another on the list of the most promising candidates is the vaccine developed jointly by the American Pfizer, the German BioNTech and the Chinese Fosun Pharmaceutical. Like the Moderna vaccine, it is based on the RNA mechanism. The results of the tests in phase I and II showed that it is safe. It also stimulates the immune system to produce antibodies at a level 1.8 to 2.8 times higher than those found in convalescents (people who have undergone coronavirus infection) and stimulates the body to increase the production of T lymphocytes (responsible for the immune response). The results of the research turned out to be so promising for the US administration that President Donald Trump signed a contract with companies for almost 2 billion dollars.
The list is closed with two vaccines created by the Chinese state concert Sinopharm, which, according to the creators’ assurances, are to be ready for sale by the end of 2020. They are the first inactivated vaccines to enter Phase 3 clinical trials on 15,000 volunteers in Abu Dhabi on July 20.
But it doesn’t stop there, because one vaccine seems to have passed a series of scientific principles. Officially, there is already one vaccine approved for use, which, despite not having passed the third phase of clinical trials, was approved by the Chinese army for use on June 25, but only by the military and only for a year. We are talking about a vaccine developed jointly by the Chinese company CanSino Biologics and the Chinese military research institute. According to the results of the Phase II study (published in The Lancet on July 20), the vaccine is safe and induces an immune response. Among the 508 volunteers from the Chinese city of Wuhan, 90% had their T lymphocytes stimulated and 85% produced antibodies.
Obviously, the above data will quickly become outdated. But they show how big the rush is for a new vaccine. However, even if one of them crosses the finish line, it will not be the end of the fight for human health.
A ruthless battle for access
Let’s assume that in the next 6-8 months, i.e. around the beginning of 2021, one (or several) of the vaccines will pass the entire registration procedure and go into production. Will they become available to everyone immediately? Unfortunately not.
According to Immanuel Wallerstein’s model, it is the core states that create the most sophisticated technologies and use them first. Other countries – semi-peripheral or peripheral – can only supply raw materials and recycle existing solutions. Later, they will also be able to use them, but they have to wait. To simplify it, we can speak of both the latest ICT technologies and medicine.
Therefore, the production of the vaccine is scheduled in six months, but in an amount that will mainly satisfy the core countries, i.e. the USA, United Kingdom, Germany, Russia, France, China, Canada and Sweden. These huge populations will be the first to get vaccinated. Some have already spent billions on the vaccine. Most also have contracts with specific companies for doses of vaccines for their citizens. Only UK has already signed a contract for: 100 million doses of the Oxford vaccine from AstraZeneca, 30 million from BioNtech / Pfizer and 60 million from Valneva. Each of them is based on a different platform, which is to give the British the best chance of having the one that proves to be effective. The Americans did likewise, securing over 300 million doses of the vaccine from AstraZeneca for 1.2 billion dollars and 100 million doses from BioNtech/Pfizer for 1.95 billion dollars, with the option of purchasing an additional 500 million doses.
In this perspective, vaccine availability for countries that do not belong to the central core and do not have several billion dollars available to fund research will be delayed and limited to key areas, including health care system employees, the most important politicians and the army. Therefore, we should not expect the immediate vaccination of the entire Polish population – rather, we will take our place in the queue, like many other countries.
Fortunately, despite the constant high number of people infected with the coronavirus in Poland, the death rate from COVID-19 is relatively low. Meanwhile, we are left to observe this race, which is more than just fighting the disease. Rather, it is similar to the struggle of superpowers for putting a man on the moon.
Polish version is available here.
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The publication co-financed by the Ministry of Foreign Affairs of the Republic of Poland as part of the public project "Public Diplomacy 2020 – new dimension" („Dyplomacja Publiczna 2020 – nowy wymiar”). This publication reflects the views of the author and is not an official stance of the Ministry of Foreign Affairs of the Republic of Poland.
dr Stanisław Maksymowicz