CORONA­VIRUS – the FAQs 4

A vaccine contains a germ (or parts of it) similar to the microbe or the virus that causes a disease. The germ has been rendered harmless after being killed or weakened. When the vaccine is injected or absorbed, our body reacts in producing antibodies similar to those observed after contact with the natural germ. These antibodies give protection and prevent the disease if we are in contact with the infectious agent. This is called immunization.

Vaccines are rarely 100% effective. There are vaccines, which provide a high level of protection to most people. Others give a partial protection but remain extremely useful in preventing the most severe forms of the disease. Some groups of people have a lower ability to build antibodies through vaccination because a disease or immunosuppressive treatments depress their immune system. The immune system of elderly people has a decreased ability of producing antibodies after vaccination. In these cases, vaccination must be discussed case by case with the patient’s doctor.

The efficacy of vaccination can only be proven by the observation of protection in the context of real life: vaccinated persons should be protected in case of a new epidemic. Taking the example of a seasonal disease like influenza, efficacy of a vaccine can only be established between October and April when the circulation of the virus is high. Vaccination must be considered as a protection not only at a personal level but also for an entire population. The interest of extensive vaccination is illustrated by the case of vaccination against measles: the annual number of cases in a region or a country is dependent on the rate of vaccinated children. The most convincing argument for the efficacy of vaccination is the case of poliomyelitis, which has been eradicated from nearly all the world with the exception of three countries where vaccination has not been rendered mandatory or accepted.

Vaccines, like medicines are tested for safety during clinical trials. In general, 10 000 to 20 000 adult healthy volunteers have received the vaccine during clinical trials before licensing. The phase one includes less than 100 volunteers and gives a first knowledge on the dose necessary for antibodies production. Phase one is also dedicated to assessing potential early side effects. Phase two will include several hundreds of volunteers followed for several months. Phase three usually includes several thousands of volunteers; the duration of phase three trials depends on the type of disease but is in general at least six months long. Phase three is of course essential in evaluation of safety, as thousands of volunteers will be monitored for potential side effects during a long period of time.

The Medicine Agencies give their approval for a vaccine after establishing a complete risk – benefit assessment of the product. Besides, health authorities monitor permanently safety of vaccines after licensing.

Nevertheless, vaccines can have side effects.
Redness and pain at the site of injection is common. A low-grade fever, fatigue and headache are also possible. These symptoms will resolve spontaneously in a few days.
More severe side effects are rare. Overall vaccination is safe and much safer than the risk of getting the disease. There has been a lot of misinformation regarding longterm side effects of vaccines, which are actually exceptional. It is now clearly scientifically proven that vaccination is not responsible for autism or multiple sclerosis.

The case of people with immunodepression is particular and some vaccinations may be dangerous for them. Their vaccination program must be discussed with their personal doctor.

Are the substances included in the vaccine safe?
Besides the dead or weakened germ the vaccine includes other indispensable ingredients needed as stabilizers. Vaccines also contain “adjuvants” needed to boost the immune reaction. Some concern has been raised about the safety of these ingredients, but they are commonly found in our environment and only present in a very small quantity in vaccines. Apart from exceptional cases of allergy, they do not provoke side effects.

One finds a lot of supposed information about side effects of adjuvants on the internet as well as about the toxicity of vaccinations but there is good scientific evidence that they are false.

The research on Covid-19 vaccine has been extraordinary intense and fast. The pandemic started in fall 2019 in China, and less than one year later there are already more than 100 vaccine candidates in development, some of them being currently in phase 3. Such a rapid development is unprecedented in clinical research. What has been done in six months, from identification of the target antigens to the manufacture of a compound and making the different laboratory tests for safety to starting clinical trials, would have taken up to ten years in a recent past!

All the strategies used by the pharmaceutical companies are aimed to produce antibodies able to block the entry of the virus in human cells. There are different approaches to achieve this goal. Some vaccine candidates use an inactivated (killed) Covid-19 virus. Another type of vaccine contains genetic material of the virus such as encapsulated Ribonucleic Acid (RNA) or Deoxyribonucleic Acid (DNA). A few other vaccine candidates are based on the injection of a part of a protein of the virus, which is indispensable for the penetration of its in human cells (the “spike protein”). Another technology consists of producing proteins of Covid-19 in order to include them in a safe virus, used as a vector to reach our immune system.

All these vaccine candidates are administered through Intramuscular injections: in general, two injections are needed.

Research on vaccines has started on more than 100 candidates. To our knowledge in August 2020 around 20 of them have entered clinical trials. A few are already in phase 3.

Considering the spread of the pandemic and the absence of curative medicine, the authorization for marketing a vaccine could be given through an accelerated process based on safety and demonstration of immunogenicity. If the Phase 3 results are positive the first license could be given at the end of 2020. There is an international competition between the companies involved in Covid-19 vaccine research. Besides humanitarian considerations, not only financial interest but also political issues are playing a role in this race.

However, there is some international collaboration in Covid-19 vaccines development, coming from the WHO, and other international institutions. For example, vaccines are developed under the auspices of the Innovations Coalition for Epidemic Preparedness, an international non-governmental organization dedicated to the development of vaccines and the prevention of epidemics.

What actions are taken by the European Union?
According to a statement issued in July 2020:
“the EU strategy rests on two pillars:

• Securing the production of vaccines in the EU and sufficient supplies for its Member States through Advance Purchase Agreements with vaccine producers via the: Emergency Support Instrument. Additional financing and other forms of support can be made available on top of such agreements.
• Adapting the EU's regulatory framework to the current urgency and making use of existing regulatory flexibility to accelerate the development, authorisation and availability of vaccines while maintaining the standards for vaccine quality, safety and efficacy.
• In order to support companies in the swift development and production of a vaccine, the European Commission will enter into agreements with individual vaccine producers on behalf of the Member States. In return for the right to buy a specified number of vaccine doses in a given timeframe, the Commission will finance part of the upfront costs faced by vaccines producers. This will take the form of Advance Purchase Agreements. Funding provided will be considered as a down-payment on the vaccines that will actually be purchased by Member States.

The related funding will come from a significant part of the €2.7 billion Emergency Support.
The EU is contributing to the global effort for universal testing, treatment and vaccination by mobilising resources through international pledging and by joining forces with countries and global health organisations through the Access To Covid-19 Tools (ACT) Accelerator collaborative framework. The Global Coronavirus Response pledging campaign raised €9.8 billion by the end of May 2020. A second step is underway in partnership with Global Citizen and other governmental and non-governmental partners, culminating in a global pledging summit on 27 June”.

Observers agree on the probability that a few vaccines could be available at the end of 2020 or at the beginning of 2021. Hopefully their protected effect will be sufficient to prevent a second major pandemic. But one must keep in mind that because of the novelty of the technologies involved in the production of vaccines and of the accelerated process of clinical evaluation, there is no warranty that they will work as well as expected. Nevertheless, there is presently no better solution available.

In theory a maximum number of people should be vaccinated in order to obtain a high (>70%) percentage of immunization in a population. But this is not realistic. Of course, strategic and political choices are not always based on scientific considerations.
Some recommendations have been given by medical societies or institutions. People who should be vaccinated in priority are:

1. Elderly people and people with chronic conditions who are particularly at risk of developing a severe form of the disease. This concerns people with chronic cardiovascular and respiratory diseases, diabetes, morbid obesity, etc.
2. Healthcare professionals
3. Care givers to most vulnerable people (elderly)
4. Professions exposed to a frequent contact with the public: teachers, public service employees, police and army personals, shops restaurants and hotels employees.

A lot of concerns have been raised about the durability of the Covid-19 vaccine.
They come from two observations. First Covid-19, like other viruses, mutates frequently. But the present opinion of virologists is that the viral proteins targeted for the production of antibodies after vaccination are relatively stable. This is an argument in favour of the vaccine’s potential efficacy. The other concern was about the magnitude and the duration of the protective effect of the antibodies against Covid-19. The monitoring of antibodies in people infected during the pandemic has brought a lot of knowledge on this matter: in summary, a majority of infected people develop protective antibodies, but their levels decrease with time at a variable rate. This situation is not exceptional in viral diseases. What will happen to antibodies produced after vaccination? The observation of the evolution of these antibodies in vaccinated people during the phase three of the clinical trials will bring answers to this important question.