Make Haste Slowly: The Race for the Covid Vaccine

POLISH VERSION

Research is currently under way on 180 or so vaccines for the SARS-CoV-2 virus which causes the COVID-19 disease. The new virus is quite similar to other dangerous coronavirus types (SARS-CoV, which causes the SARS epidemic in 2002, and the MERS-CoV discovered in 2016), which allowed scientists to ramp up the research into the vaccine by using the knowledge of the two prior viruses.

However, important questions linger about safety and effectiveness, especially in a long-term perspective. The greatest fears naturally concern the amok pace and process of testing the new vaccine. And it is undisputedly very rapid. It is even shorter than the process of testing any drug which takes years of clinical trials to be granted its official authorization. The proof of effects of the short time for testing is an example of one of vaccines. As its creators admit, the reason they chose the specific dosage scheme for the candidate vaccine was “a fluke”. It simply happened so that someone made a mistake and gave some of the trial patients a first dosage too low, as Reuters reports. It was “by chance” that one half of the first dosage was beneficial to the efficacy, unlike the less effective two full doses. The current circumstances are indeed extraordinary, but it does not justify resignation for the care for safety of billions of people around the world.

Why is finding the cure so important?

The human organism is protected against viruses by its immune system. There are two lines of defence. First is the non-specific immunity, which prevents pathogens from entering the human body with natural protective barriers (like the skin) and ‘devouring’ of the ‘invaders’ by macrophages, a.k.a. “scavenger cells”. This immunity system type can stop most of bacteria and viruses which attack our body.

Sometimes, however, the sheer count of pathogen is overwhelming enough to penetrate into the human system; some pathogens feature dedicated defence mechanisms to achieve the same objective. This is where the specific immunity comes in. It is a more specific defence strategy which the human body must “learn” against each pathogen. For example, when a virus is ‘devoured’ by a macrophage, the macrophage digests the virus after which its molecules are presented on the macrophage’s surface. This engages other immunity cells. They are T-lymphocytes. Their primary function is to identify the viral molecule as “alien” (also known as an “antigen”). Next, T-lymphocytes destroy the cells which carry the antigen of the virus on their surfaces. On the other hand, T-lymphocytes have another function: they “display” the previously “memorized” antigen to other cells, B-lymphocytes. B-lymphocytes respond by producing antibodies, which are immunity proteins which attack the virus. This complex response cascade results in long-term resistance to the virus, and sometimes the resistance could last a lifetime.

SARS-CoV-2 is a virus known to inhibit non-specific immunity. Hence, in the first stage of infection, it can multiply liberally, avoiding macrophages and production of antigens. It is curious that the first infection symptoms of the SARS-CoV-2 virus become evident after a long time (which is 2-12 days on the average, whereas the influenza virus triggers symptoms in 1-4 days). The disturbed immunity response may also contribute to the poor condition of patients who run COVID-19 grievously.

A vaccine like a USB thumb drive

One of the main threats in the course of COVID-19 is the delayed response of the immunological system. It is a reason why preventive inoculation is used to protect human bodies from viruses. Preventive vaccines apply the natural mechanisms of specific defence by exposure of the human body to, respectively: (1) inactivated viruses; (2) viral proteins; (3) DNA; (3) mRNA (messenger ribonucleic acid).

Currently, the champions of popularity are mRNA vaccines (manufactured by Pfizer and Moderna, for example), which are relatively simple and quick to make, especially when compared to traditional inactivated virus vaccines. mRNA vaccines are made without using animals or cells, they require standard chemical reactions in a laboratory setting. Administering the mRNA molecules made so to the human cells enables synthesis of the protein of the characteristic ‘spikes’ of the virus, which, in an actual viral infection, attach the virus to the attacked cell and enable transport of the pathogen’s genetic material inside.

More importantly, the mRNA molecules administered in a vaccine cannot become permanently embedded into the cell’s genome and thus no genetic modification (as in GMO) is possible. “It is more like a USB device (the mRNA) that is inserted into a computer (your body).  It does not impact the hard drive of the computer but runs a certain program,” Tal Brosh explains, head of the Infectious Disease Unit at Samson Assuta Ashdod Hospital, Israel. There is no actual virus produced, too, since the resulting protein is ‘digested’ by the macrophage and presented on its cell’s surface. The effect is the production of antibodies is triggered to protect the system from the attack of the real virus. mRNA vaccines are now generally believed to be safer than other vaccine types.

The drawbacks of leading vaccines

As any invention, mRNA vaccines do not come without weaknesses. Among the chief problems is that mRNA molecules are very sensitive to changes of temperature. They require storage at extremely low temperatures (-70^oC, as is the case with the vaccine from Pfizer/BioNTech) or application of a suitable vector (like inactivated adenoviruses in the vaccine from Moderna and the Russian vaccine Sputnik V).

The application of an adenovirus, which is a common cold virus, may raise objections. Scientists point out that specially modified viruses are used which do not cause any disease, but merely serve as transport vessels for the mRNA payload and as such they are supposed to be perfectly safe.

As any invention, mRNA vaccines do not come without weaknesses. Among the chief problems is that mRNA molecules are very sensitive to changes of temperature. They require storage at extremely low temperatures

A logistical challenge

The low storage temperature of the vaccine is a very serious logistical challenge. However, it is crucial for successful vaccination. The level of preparedness of the Polish healthcare system for the process triggers considerable doubts. Unfortunately, it happened more than once that even less demanding drugs suffered hazardous interruption of the cold chain.

Another issue is that the duration of the immunological effect is unknown. Experts note that there is not known how long the immunity from the vaccine will be, will the vaccine also protect seniors and immunologically deficient patients, or if the produced immunity will inhibit the virus from spreading or simply restrict the progress of the disease in those inoculated.

Unfortunately, the brevity of third-stage clinical trials will most likely have us waiting for the answers for months, if not years. However, note that the research into the mRNA vaccines should continue after they are launched on the market and we can be confident that they will be continuously improved. It is the promise of the makers of the vaccine from Moderna. In the meantime, we can expect more vaccines to emerge, possibly with other antigens.

100 days of blowing smoke

The challenges presented here should be considered when implementing a general inoculation scheme. It is beyond any doubt that vaccination is our primary weapon against COVID-19. Inoculation saved humanity more than once and we stand very hopeful about their efficacy once again. What causes doubt is the way in which the efforts to make the vaccine for the coronavirus evolved into a geopolitical race for primacy. It is why the vaccine, which is to be administered to millions, or perhaps billions must be absolutely free from any suspicion of having been tested sloppily or from immunological response instability. It is a tool of medicine, not politics. Should the vaccine fail, it will ravage the already shambling general disease prevention.

In the light of scientific pondering, even generic vaccines which have never been tested on a large scale seem to be successful. In biological analysis, their safety profile seems to be very good.

However, it needs to be reined in somewhat, this PR applause with which the governments around the world have used a medicinal formulation to manage their constituents. If vaccination is indeed to take the load off the healthcare systems, it must be widespread. In Europe and the USA alone, there are hundreds of millions of people who will need at least two vaccine shots to produce a meaningful immunological effect. The assertions of one of biotech companies that it will make 1.3 billion doses of the vaccine by the end of 2021 are good for roughly 600 million people. Is it much? It is far less than the population of the EU and the USA combined (approximately 770 million people). Moreover, the vaccination is to be done in batches throughout the whole next year and will not begin already in spring, as official communications suggest. There are other biotech companies in this race and the number of vaccines could be higher after all. However, they will vary in efficacy profiles, administration regimens, and availability. The price will also be a variable, since the potential revenue of vaccine producers are exorbitantly high and one of the prizes of the race. Ironically enough, the demand for the remedy to COVID-19 is so high that even the vaccines of poor efficacy will have takers. They must be safe at least.

It must be said clearly that those “100 Days of Responsibility” promoted by the Polish government and after which the outbreak will end thanks to popular vaccination will, in reality, apply only to narrow sections of the population, like seniors, healthcare workers, and uniformed services. Other citizens will most likely have to wait for their shots several hundred days more.

In this perspective, the political game based on vaccination will only undermine trust for the authority. It will also put the increasingly popular anti-vaccination movements in a higher gear. The situation might get out of control after all. It is difficult to enforce restrictions already while the trust for the authorities is spiralling to a crash. There is a growing number of the COVID-19-afflicted who hide their condition in fear of ineffective, non-transparent quarantine and treatment mechanisms. Can the Polish government convince millions of citizens to take a shotful of hastily designed drug as things stand?

Translation financed by the National Freedom Institute – Centre for Civil Society Development from the Civil Society Organisations Development Programme for 2018-2030

Tłumaczenie sfinansowano przez Narodowy Instytut Wolności – Centrum Rozwoju Społeczeństwa Obywatelskiego ze środków Programu Rozwoju Organizacji Obywatelskich na lata 2018-2030