"Should I get the vaccine...?"

In the famous game show "Who wants to be a millionaire?", the player, after answering a series of questions correctly, is asked to answer the crucial last one that will make him/her €1,000,000 richer. Our title question could be the crucial question, but the prize is not money, but health. A prerequisite, of course, for giving the right answer is that there is a right answer.

We are referring, of course, not to just any vaccine, but to the vaccine against the SARS-COV-2 virus. It became clear very quickly - already during the first wave of the pandemic - that the treatment of the virus would be based on the discovery of a vaccine, not a drug. Indeed, drugs such as remdesivir, hydroxychloroquine, dexamethasone, monoclonal antibodies, act as adjuvants, but are far from being considered a cure, especially for the severely ill. Thus, the R&D effort of many pharmaceutical companies, with the assistance of universities and independent biotechnology laboratories, has rapidly turned to the production of vaccines.

Currently, there are 214 trial vaccines under development in various phases, with 10 of them in the third and most critical phase. Vaccines, like any pharmaceutical product, need to meet objectives and overcome hurdles on three levels : 1) efficacy (doing what it promises), 2) safety (having no serious side effects in the short and long term) and 3) large-scale production. The processes required are so laborious, costly and complex that the fact that in less than a year we are so close to producing the first vaccine borders on the miraculous. The corresponding approval times for the Ebola vaccine were 5 years, for measles 9 years, for HPV 15 years, for polio 20 years!

In this frantic battle against time, 2 vaccines developed with the pioneering mRNA technique currently seem to be ahead of the game. Which is it? The job of vaccines is to activate the immune system. The traditional approach is to inject into the human body a weakened version of the virus or inactive parts of the virus (this is followed by e.g. the Oxford vaccine, the Russian SPUTNIK V and others). With the new method, the vaccines transfer a part of the virus' genetic code (mRNA) into human cells and the cells themselves produce some components of the virus, e.g. glycoprotein spikes. These safe components then activate our immune system and immunity develops. As you can see, with this process, the physical presence of the virus is not even needed, only the decoding of its genome.

Is it really a new discovery? No. In fact, it is based on the efforts of a relatively unknown researcher, Katalin Kariko, who has been researching the potential of mRNA since the 1990s, facing years of constant rejections and failures. But her persistent efforts - they could be the script for a movie - have been the foundation for the establishment of biotech companies, such as Moderna and BioNTech, which are leading (and competing) in bringing these vaccines to market. Perhaps here it would be worth shedding light on some of the more obscure aspects of our topic by saying a little about these two companies.

Moderna, although it has been in existence for about a decade, having raised over $2 billion in capital, has not launched any drug molecules. But having the mRNA know-how, just 42 days after decoding the genetic code of the virus, it produced the test vaccine (24 February). On 28 July it was the first to start phase III trials and, without releasing any data, as early as 18 May it announced 'positive preliminary data'. Its research was funded by the Trump administration, which has pre-agreed to purchase 100 million doses for $2.48 billion. It has been heavily criticised because its executives have sold tens of millions of shares.

BioNTech was also founded around the same time, by a couple of Turkish researchers in Germany. In all these years it has not received approval to market any of its products (there are 13 under approval). It has attracted more than $3.5 billion in funding, the main partnership being with Pfizer, which will produce and market the vaccine. It has refused to receive funding from the US government, but has agreed to sell 100 million doses for $1.95 billion. Just last week, Pfizer's Greek CEO, Albert Bourla, announced preliminary phase III results that have been met with excitement, showing efficacy of over 90%. Immediately, Pfizer shares hit an all-time high.

A detail common to both companies: their efforts so far to produce various other mRNA pharmacomolecules have mainly stumbled on their antigenicity at therapeutic doses (as did Katalin Kariko's earlier efforts). This now seems to be circumvented in the case of 2-dose vaccines.

But who ultimately guarantees the safety of vaccines? First of all, the researchers themselves. Although, as is obvious, this is a race with a prize fund of several billion, we cannot question the ethics of top scientists, nor the fact that a 'bad' drug ultimately results in a loss for the company producing it. That is why, after all, the process of clinical trials involves multiple safeguards. Whether they work as intended is checked by peer reviewers and ultimately by the authoritative approval bodies(FDA in the USA and EMA in Europe). As these are normally time-consuming and exhaustive procedures, the crucial question is whether and to what extent the checks will work as normal or whether there will be 'discounts' due to the unprecedented urgency of the situation. It must be admitted that there has been no shortage of undue pressure for the approval of vaccines: the election pledges of the outgoing US President, the 'nationalisation' of various vaccines, the advertising of their effectiveness without the completion of studies, the constant pledges of 'expert' professors with no data and no real knowledge of the subject, with release dates that are constantly being contradicted. In this truly pressurised environment, therefore, we are called upon to answer the 'million dollar question':

Finally, should I get the vaccine? I honestly believe that the problem with the critical question is the question itself. Are we talking about a vaccine (conventional or mRNA) that needs to be given to save the careers of some politicians, to boost the national morale of some countries, to give prestige to some "know-it-all" professors? Are we talking about a vaccine that should not be given because it serves economic interests, it is unnecessary because we will get immunity anyway, it contains a microchip? Or are we talking about a vaccine with a full dossier, published data, evaluation and approval by real experts, with reporting and quantification of side effects and efficacy, with at least an admission of weaknesses in long-term predictions (which is in fact the case with every drug)? And since the candidate vaccines are a few dozen and disparate from each other, who and how will ultimately decide which vaccine we are talking about?

With all this in mind, I believe that at this particular moment in time, without any intention of evasion, the only responsible and correct answer is: "I don't know"! Or more precisely, "Idon't know . yet". Fortunately, the scientific tools to say yes exist and I hope that they will be given to us very soon in a transparent and clear manner. Vaccination as a practice is one of the greatest achievements of medicine, having saved the lives of countless children and adults, and the first official data allow us to be optimistic. It will be a real shame, when the time comes for a personal decision to be taken by each of us on the basis of unsustainable and unscientific criteria. You see, in the famous game show, the wrong answer is only the loss of money. But here we are talking about health, about life itself!

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