In Search of the Hopeful COVID-19 Vaccine. Who will Win the Race to a New Normal?

Introduction

We are all aware that about four months ago everything worked differently than it does today. Some people have not yet reflected enough on what has happened, and why not venture to say, it will continue to happen; this is not yet over. The world has changed in many things, and these changes have been very noticeable, in such important structures of society as social and health. Healthcare workers have been heroes, fighting bravely against all odds, exposing themselves to infection without protective equipment and working tirelessly to bring infected people forward (Yan et al., 2020; Zou et al., 2020).

The world of information and news has allowed society to keep up with the evolution of the pandemic that is happening to us at the moment through the evolution of the coronavirus COVID-19. On the contrary, there has also been a lot of infotoxication, mainly due to the excessive use of social networks to which all users are exposed and use worldwide.

The information has had to be filtered, and at times, it has been us who, at certain moments, almost out of desperation, have changed a certain piece of news according to our convenience, probably trying not to fall into discouragement in the face of the events of the new pandemic. Its rapid expansion due to the number of infections has led us to situations of overflow as has happened in many health centres and retirement homes, taking measures that we would never have thought of. We are talking about a virus that does not discriminate by gender, sex, ideology, territory, cultural level, religion, and so on, we are talking about a virus that has been able to take humanity almost against the ropes in some moments (Gorbalenya et al., 2020; Guan et al., 2020; Heimdal et al., 2019; Meyer & Christie, 2013).

The confinement of the population has achieved positive things, since by reducing the use of vehicles, the rates of environmental pollution in the cities have been reduced, even if only temporarily, and the ties within the family nucleus have also increased, however, there have also been situations of stress and loneliness in part of the population (Sanglier et al., 2020a).

The pandemic has forced us to reorder our time, to slow down, perhaps this is also a good thing. We are responsible for the education of children who have also been forced to change their habits. The way of working has been changed and teleworking has been incorporated to a greater extent, perhaps with it human relations with friends and family, in the long term, being more impaired (CDC, 2020). But you learn to value more what you do not have.

Society, in general, has had more time to think collectively, to respect confinement measures for a common good, to work together on the issue of opening borders between different countries, to be able to identify transit zones between their communities and to take care to keep the infected persons identified so that the effect on the population is as small as possible.

Each affected country has implemented the measures it has deemed most appropriate, there have been many countries affected in Europe, after the infection started in China (Wu et al., 2020a, 2020), now those countries are recovering, and the infection has advanced to other continents in an alarming way such as Latin America and South Asia. The numbers of people infected and killed by the pandemic are soaring in these areas.

SARS, or severe acute respiratory syndrome, killed 774 people in 17 countries. These outbreaks had mortality rates of 9.5% and 34.5%, respectively (Ding et al., 2003; Li, 2005; Peng et al., 2006). The coronavirus that started in Wuhan has so far caused a number of people infected with COVID-19 worldwide of about 7.5 million people, and a number of deaths of about 420,000 people. Currently, there are about 188 countries out of 194 infected, which means a level of infection of 96.9% of all countries in the world. The countries most affected by the pandemic so far are the United States, Spain, the United Kingdom, Italy, France, Germany, Russia, Turkey and Brazil, where the number of deaths has exceeded 100,000 (WHO, 2020).

It is time to reflect and join efforts in the same direction, to connect, to think logically, to feel, to reflect and to forget values in order to achieve a common goal, to get a vaccine as soon as possible and to put the virus against the ropes, before the virus puts us (Scagnolari et al., 2004; Tian et al., 2020). It is a battle against time, a battle that we can and will win, but as a rule and according to the data of the last few decades, it seems that every four or five years there are outbreaks of viruses that we may not be able to defeat in time, humanity is at stake, and time is golden now, let us make our way little by little but lay the foundations for a future that tends to be very dangerous. Perhaps we have realised that investing in science is investing in a safer future, a future from which a more promising and committed world can be glimpsed. Now it is time to find the saving vaccine that will make us return to the new normality of life, perhaps never again, but it is better than never returning to anything (Chen et al., 2004; Chu et al., 2018; Hoffmann et al., 2020; Morgenstern et al., 2005; Ng et al., 2008; Yang et al., 2004).

Methods and Materials

A study will be conducted on how the different developments of COVID-19 vaccines are going in the countries that are at the forefront of their development. It could be said that almost from the initial moment of detection of this pandemic, different laboratories around the world have been studying and looking for a vaccine to counteract the effects of this new type of coronavirus (Lin et al., 2003, 2020).

Its symptomatology has been studied and it has been seen how it affects people who suffer from it. The most serious symptoms that have been diagnosed are a fragilisation of the lung tissue into an inelastic tissue with a feeling of shortness of breath or air, chest pain or pressure, and an inability to speak or move. Other less common symptoms that have been detected include: dry cough, small tumours in the upper and lower extremities, fatigue, sore throat, diarrhoea, conjunctivitis, loss of sense of smell or taste, headache, diabetes, skin rashes, or loss of colour in the fingers and toes (Cheng et al., 2020; Corman et al., 2018; Dahirel et al., 2011; Fu et al., 2020; Huang et al., 2020; VijayKrishna, 2007; WHO, 2005a, 2005b)

In the face of this pandemic, the scientific community is acting in a coordinated manner and with sufficient resources to find a vaccine as soon as possible. More than a hundred projects are currently being developed, some of which are already at an advanced stage.

Conclusion

As can be deduced from the above study, the leading research centres in Virology, Pathogens and the study of rare diseases are fighting to find as soon as possible a vaccine that can, for the time being, bring humanity to safety. At the moment, hopes are pinned on five Chinese research centres, four American, one British and one German, as the leading or most advanced centres in terms of clinical sub-phases applied to arrive at an effective and safe vaccine definitively.

From what has been analysed so far, the most advanced centres are in sub-phase 2 and are a Chinese centre (Institute of Biotechnology) and an American one (Modern/National Institute of Infectious Diseases (NIAID)). There are five other centres between sub-phases 1 and 2, and the remaining centres (three) at the forefront of research to achieve the final vaccine are in sub-phase 1.

Apart from vaccines, which will still take some time, drugs are another possible short-term solution. There are some drugs where their safety has already been proven, among them are Remdesivir (Ebola), the only one already in clinical phase 3, prior to commercialization; Lopinavir and Ritonavir, Hydroxychloroquine and Chloroquine (malaria). However, according to clinical data, the latter two drugs do not appear to provide any benefit over patients treated with COVID-19. In view of the doubts generated, the WHO has decided to suspend all its hydroxychloroquine trials while the risks are reviewed.

There are other drugs whose development is based on antibodies and where several researches worldwide focus their efforts on identifying proteins that prevent the SARS-CoV-2 virus from parasitising human cells and using them to replicate its genetic material. Two independent laboratories, one in the Netherlands and one in Israel, have already obtained antibodies capable of neutralising it, following the example of other diseases already treated with this same technique.

One of the measures to see the number of people infected by the virus, has been the vaccination of a part of the population to which are added the people who are immune because they have developed antibodies after a previous infection, this is called ‘herd or collective immunity’, which provides indirect protection to the non-vaccinated individuals.

Epidemiologists estimate that 60%–70% of the population needs to be immune to the virus to achieve this kind of collective immunity.

Until the vaccine arrives, there are very conflicting positions on taking action. There are advocates that contagion should occur freely without putting in place any measures to combat it, with the intention of increasing herd immunity in the population. This allows an increase in the number of positive cases and in the number of people circulating to increase the generation of antibodies and the creation of an immune barrier. But this strategy does not seem to be a good solution, as it could lead the health system to a situation of collapse, and consequently, to the death of a large number of patients.

In Spain, the first data from the seroprevalence study carried out by the Ministry of Health are quite discouraging in this regard. Only 5% of the Spanish population would have generated antibodies, so this ‘herd immunity’ without a vaccine seems an extremely difficult horizon to reach, especially considering the high human, health and economic costs that such a low percentage has implied.

Who will reach the goal first, is a dilemma that we hope will soon have a solution, the important thing is to reach that goal that for now seems a little distant.

Discussion

The fact that only 5% of Spaniards have been in contact with the most destructive pathogen of this century leaves citizens at the mercy of the discovery of a vaccine: the only thing that could guarantee the famous herd immunity, and that most people could return to normal life without the risk of infection. In this race against the clock in which there is no limit to the number of participants, there are several major obstacles. Overcoming them will be necessary so that the desired immunization can be given to healthy people.

Now vaccines cannot or should not be developed that would be counterproductive for the population, as was the case in 1996 in the United States, where the first vaccine against the respiratory syncytial virus was tested, because controls are very demanding. This is something that slows down the process, but it is necessary. A vaccine is not given to repair the damage, but to prevent it. This means that the sample sizes for testing have to be much larger than those used in the drugs.

There are four main vaccine routes to combat the new coronavirus, one using attenuated virus, one using recombinant DNA, one using RNA and one based on recombinant purified antigens. The new vaccines are never easy to obtain, it is a very complex biological product, and the research capacity is what it is.

Although the results could be encouraging, there are groups of scientists who have reached sub-phase 2, many more experiments have to be performed, to analyse how the immune system is stimulated, to see the correlation between the different parameters of protection against the virus (protective correlates). Antibodies and cellular immunity have to be studied. Currently, there is very interesting work regarding the cellular immunity that induces SARS-COv-2 infection and that is very relevant when designing vaccine candidates.

We also have the problem of the circulation of the virus, it could be that it circulates little or not at all when it comes to demonstrating its effectiveness on a large scale. One possible solution, this has been suggested before, would be to purposefully infect volunteers in a controlled way, this is a very controversial open debate especially for a disease for which there is no treatment, with very serious complications even with death of the patients, and there are many ethical aspects to consider.

A bet could be made to start vaccination in high-prevalence areas and see if vaccinated individuals do not get infected or get infected only very mildly. This type of procedure is usually followed to test vaccines such as tuberculosis. It is initially studied in volunteers to assess toxicity, but the successive clinical phases are done in countries with high incidence. Groups that are vaccinated are then compared with groups that are not, and the percentage of people infected in each group is analysed.

Assuming that the first part of development is overcome and a prototype of the COVID-19 vaccine will soon be available, we are now entering the production part. You’d have the brake on mass production. Despite advances in pharmaceutical R&D, the technology has been around for many years and has not evolved much. The time it takes to develop the product, once you have it, and to manufacture it remains the same. It is estimated, objectively, that the time to achieve a large-scale vaccine with millions of doses will be between 14 and 18 months from the start of the research. This ‘long time’ could be solved with alliances and business clusters that could use multi-dose vials among other solutions. The antigen should be produced in GMP (good manufacturing practice) companies, but this, in turn, could trigger a ‘bottleneck’.

Recently, outbreaks of the new coronavirus have begun to be detected, suggesting that the factor of speed in the manufacture of the vaccine is becoming increasingly important. You can choose to start making it before you know if it is effective as researchers at Oxford University have done in human clinical trials.

The pharmaceutical industry seems to have committed itself to produce it on a large scale while it is in sub-phases 1 and 2 of development. However, a pharmaceutical product can only be legally manufactured when it reaches sub-phase 3, which includes a clinical trial in humans. Ideally, the technology should generate faster product development, which is scalable and cost-efficient. The future points to recombinant proteins, which are the drugs of the future, however, the technologies applied to produce them are always based on bioreactors, which are very complex and expensive facilities.

We enter a phase where we have to weigh up the speed in order to get the required information as soon as possible to first select from the vaccines that are being developed which one of them can be more or less effective, without ignoring the safety of the vaccine. In a rush, there is always a possible decrease in vaccine safety. In this case, the risk/benefit of protection must be assessed. At this moment, the processes are being speeded up in a very important way, especially skipping the study in animal models and going directly to test in humans.

Even if the steps in the development and production of the antigen are shortened, there are other difficulties to be taken into account. There might be a logical temptation for the country that finds the vaccine first to want to vaccinate its population first, but to avoid this are the institutions. One could consider giving priority to the administration of the vaccine, in the country where the virus is circulating at that time. It is estimated that about 7 billion doses would be needed immediately; assuming that one dose would be sufficient and that other types of vaccines would be discontinued. WHO is expected to be the agency that provides order and sanity in the delivery and distribution of vaccines.

To provide the vaccine at the same time and to everyone seems an impossible task, so priority should be given to the most vulnerable population, to the health workers and the elderly, perhaps also to the state security forces. But it would depend on the characteristics of the vaccine, because it might work, for example, better in the young population.

The economic issue also plays an important role, some politicians are betting on a shared risk, that is, that the governments contribute economically to the development and production of the vaccines, risking to be betting on a product that finally does not work. It must be taken into account that the development of a vaccine from its initial phases is very costly in terms of time for experimentation, and in its implementation, passing through the different clinical phases required for final approval by the regulatory agencies, in addition to the added cost of producing the vaccine.

The cost of the vaccine will depend on the type of vaccine you have. If the pathogen is attenuated, for example, it has to be grown under GMP conditions, it may not grow well, it may have to be repeated. You have to look for cells that can be infected by a particular virus, and not many companies can manufacture this type of vaccine. It must be taken into account that the safety and regulation conditions are very extreme to work with pathogens. It can also happen that the successful vaccine is developed with protein, DNA, and RNA components. In that case, the type of production is different, of course also under GMP conditions, but in a different way, and it is usually other types of biotechnology companies that could develop them. It is also necessary to see what kind of adjuvants are used, and what kind of combination is finally used. These are certain conditions that must be taken into account, he specifies.

All these reflections lead to the conclusion that the important thing, in the end, will be to reach the goal and get the right vaccine so that humanity, this time, will be safe. What will happen next? We do not know, but what seems to be true is that this time the work has been done side by side, that the work has been done differently and that the efforts of many scientists from all over the world have been united, sharing more than other times, to achieve the common goal, to find the COVID-19 vaccine.