Based on the innovative messenger RNA technology, the Pfizer vaccine received its marketing authorization from the European Union on 21 December 2020.
In France, the first doses injected, in elderly patients, the most at risk of developing a severe form, began on December 27, 2020. In total, 600 million doses of the Pfizer BioNTech vaccine have been ordered by the European Union for the year 2021.
This reveals a 95% effectiveness in preventing severe forms of Covid-19, but this effect may decrease in mutated viruses, called variants.
Context of Covid-19 vaccination
It was at the end of 2019 that the first cases of a new respiratory disease quickly baptized Covid-19, appeared in China, in the city of Wuhan.
Caused by a coronavirus, SARS-CoV-2, this emerging pathology has spread around the world, causing a pandemic that has caused many deaths, and has caused several periods of confinement in many parts of the world.
In France, at the end of August 2021, the High Authority for Health counted a total of more than 114,000 deaths. In addition, long forms of the disease also appeared, causing symptoms that can persist for several months, even in relatively young subjects and without comorbidities.
It is in this context that the first vaccines appeared in the course of 2020. And so, Pfizer, an American laboratory founded in 1849 and which currently has nearly 92,000 employees worldwide, has partnered with the German biotechnology company BioNTech, created in 2008, to launch the very first vaccine against Covid-19.
What is the principle of the Pfizer vaccine?
Operation and principle of action
The Pfizer-BioNTech vaccine is called Cominarty. It is a vaccine based on messenger MRA technology, an innovative technology that is based on a long scientific history: indeed, researchers have been working on the subject for several decades.
Usually, the principle of a vaccination is to inject an attenuated or inactivated form of an infectious agent or some of its components into the body. The goal is, thus, to prepare it for further contact with a pathogen. Indeed, this vaccination causes the development of immune cells called 'memories', which will immediately recognize the pathogen if the individual were to be exposed to it naturally.
What is a messenger RNA vaccine?
The principle of these new so-called messenger RNA (Ribonucleic Acid) vaccines is a little different since they consist in making the fragments of infectious agents produce directly by the cells of the vaccinated individual. It is therefore not, in this case, the virus in its attenuated form that injects, but only the RNA molecules encoding proteins of the pathogen. The cells that are located near the injection site, essentially muscle cells and cells of the immune system, will then make the proteins of this pathogen themselves, in this case, fragments of the Spike protein. These were chosen upstream because they trigger a significant and protective immune response.
In fact, the Spike protein is indeed a key molecule of SARS-CoV-2: present on its surface, it allows the virus to cling to cells before penetrating and then infecting them.
The Pfizer BioNTech vaccine induces both neutralizing antibody production and cellular immunity in response to the Spike antigen produced by the body's cells from injected mRNAs.
Composition of the vaccine
The vaccine is therefore made up of messenger RNA fragments, which are transported by lipid particles to the right place, inside the cells of interest. These nanolipid particles that carry vaccine messenger RNA have a composition similar to that of lipids located in the membranes of all cells of our body and therefore pose no risk.
In addition, RNA is, like DNA, a molecule naturally present in all cells of living beings. Indeed, DNA, which is located in the nucleus, carries the genetic heritage of any individual. As for RNA, it is synthesized from DNA fragments and is used as a pattern by complex cellular machinery (including ribosomes), to make all the proteins necessary for the functioning of the body.
Choosing an RNA vaccine over a DNA vaccine
This choice is important: indeed, it allows the Spike protein to be produced directly in the cytoplasm of the cells of the vaccinated person, that is to say by the part of the cell that surrounds the nucleus, and thus prevents this molecule from entering the nucleus. These vaccines are potentially better tolerated since they do not rely on whole viruses. In addition, they do not use any adjuvant, but only nucleic acid molecules (the famous RNAs). The RNA contained in the vaccine will thus play a dual role: to express the viral protein and to stimulate the immune system without adjuvant.
This messenger RNA is produced using cells in vitro transcription from the corresponding DNA matrices and encoding the viral Spike protein of SARS-CoV-2. The drug is provided in a multidose vial. It should be diluted before use: for this reason, one 0.45 ml vial contains six doses of 0.3 ml after dilution. One dose, or 0.3 ml, contains 30 micrograms of mRNA vaccine encapsulated in lipid nanoparticles. The vaccine also contains excipients.
Who can receive the Pfizer vaccine?
Children over 12 years of age and adults
Adolescents between the age of 12 and 18 as well as adults can receive the Pfizer vaccine.
Marketing authorization in Europe was granted on 21 December 2020 for all adults and adolescents over 16 years of age. This MA has been extended to adolescents aged 12 to 15 years from 10 June 2021. In France, the HAS issued a favourable opinion on 3 June 2021 for the use of this vaccine among adolescents between 12 and 15 years of age. The overall safety profile in adolescents assessed in two clinical studies involving a total of 22,975 participants was similar to that observed in participants aged 16 years and older.
Seniors and over 55 years of age
Advanced age is the main risk factor for severe Covid-19 and therefore hospitalization. However, the Phase 3 clinical trials that led to the commercialization of these vaccines were under-represented of older people. The first French data published on May 21, 2021 by EPI-PHARE (public expert group in the epidemiology of health products) on the effectiveness of the Pfizer-BioNTech vaccine show an effectiveness that seems excellent in elderly subjects, with a protection rate of at least 90% for 75-85 year olds and at least 80% for those over 85 years old.
Pregnant women
According to data from the World Health Organization (WHO) updated at the end of June 2021, pregnancy puts women at a higher risk of severe Covid-19, but currently, very little data exists to assess the safety of the vaccine during pregnancy.
Pregnant women at high risk of exposure to SARS-CoV-2 (e.g. Health workers) or with comorbidities that increase the risk of developing a severe form of the disease can be vaccinated in consultation with their caregiver. Thus, in pregnant women, the vaccine should only be considered if the potential benefits outweigh the potential risks to the mother and fetus. The website of the Ministry of Health indicates a possible vaccination for pregnant women from the second half of pregnancy.
People with comorbidities
For the WHO, "the Pfizer BioNTech vaccine has proven its safety and efficacy in people with different conditions associated with an increased risk" of the severe form of the disease.
Among these co-morbidity factors are mentioned:
- high blood pressure;
- diabetes;
- asthma;
- lung diseases;
- hepatic or renal;
- as well as chronic infections under control.
Are there any precautions for use and contraindications?
Prevention
The vaccinated person should be monitored for fifteen minutes after vaccination. In addition, a second dose should be avoided in the event of an anaphylactic (i.e. Allergic) reaction that occurred following the first dose.
Contraindications
The Pfizer BioNTech vaccine is contraindicated in case of hypersensitivity to the active substance or to any of its excipients.
For information, here is the list of excipients contained in this vaccine:
- ALC-0315, ALC-0159, DSPC;
- cholesterol;
- potassium chloride;
- monopotassium phosphate;
- sodium chloride;
- disodium phosphate dihydrate;
- sucrose;
- Water for injection.
What is the dosage of the Pfizer vaccine?
What is the recommended duration between the 2 injections?
If a protective effect begins to appear twelve days after the first injection, two injections are necessary to ensure complete protection. The recommended duration between the two injections, according to WHO recommendations, is 21 to 28 days.
In fact, in France, the usual time between the two injections of the Pfizer vaccine varies from four to six weeks, but during the summer of 2021, this interval was able to extend from three to seven weeks.
Should you get vaccinated when you have had Covid-19?
The High Health Authority indicated, in an opinion issued on 11 February 2021, that people who have already had Covid-19 can be given a single dose of vaccine. Indeed, people who have already been infected retain an immune memory. Thus, this single dose of vaccine, therefore, plays the role of 'booster' following infection.
In addition, people who have received the first dose of vaccine and who have coronavirus infection (PCR, antigenic or serological test positive) should not receive the second dose within the usual time frame. They must wait at least two months after the end of the symptoms before proceeding with the vaccination.
Third booster dose: why is it recommended?
After analyzing the available data, the HAS published on August 24, 2021, an opinion: it recommends a booster dose, the injection of a third dose with an mRNA vaccine, for people aged 65 and over as well as for people with comorbidities because these increase the risk of presenting a severe form of Covid-19. In fact, this booster dose will be administered after a period of at least six months following the primary complete vaccination.
The HAS justifies this decision given that "recent studies suggest a reduction in the effectiveness of all vaccines, especially against the delta variant". In addition, "the decline does not only affect the elderly and populations at risk of severe illness, but the latter remains the most affected". This opinion of the HAS was issued at the request of the government to allow the organization and anticipation of the recall campaign. However, it remains conditional on the validation of this recall by the European Medicines Agency. Finally, the third dose is also indicated for highly immunocompromised people.
How is the Pfizer vaccine stored?
The Pfizer BioNTech vaccine can be stored for six months at very low temperatures, between -60 and -90 degrees.
Pfizer has created a thermal container: it guarantees the safety of its vaccine during transport and storage, at a temperature between -25 and -15°C for a single period of up to two weeks and can then be returned to a temperature of -60 to -90°C. When thawed, the uninsured vaccine keeps between 2 and 8 degrees for a month. Before use, the unopened vial can be stored for a maximum of two hours at temperatures up to 30°C.
Is the Pfizer vaccine effective?
Protection against covid-19
The protective efficacy of the Pfizer vaccine in preventing Covid-19 is estimated at 95%. As with any vaccine, not all people vaccinated with Cominarty may be protected. It takes seven days after the injection of the second dose of vaccine before the vaccinated persons are optimally protected. Estimated efficacy values have similar values based on gender, ethnic group, as well as in vaccinated individuals with comorbidities associated with a high risk of severe Covid-19.
The duration of protection conferred by the vaccine is not established. It is still being evaluated.
A study conducted in Israel
A study on the data of nearly 600,000 people who received the Pfizer-BioNTech vaccine versus a control group of as many people was conducted in Israel, a country that began its vaccination campaign quickly and has significant coverage of its population.
This study confirmed the high efficacy of this vaccine. Thus, a week after receiving their second dose of vaccine, a person is ten times less likely to be unknowingly infected and potentially transmit the virus. But the major result of the study is the demonstration of a drastic reduction in mortality: indeed, it is reduced by 72% two to three weeks after the first dose and one week after the second dose, no deaths have been recorded.
Protection against variants
The SARS-CoV-2 genome, like that of other coronaviruses, is made up entirely of RNA. This sequence of four nucleotides (adenine, guanine, cytosine and uracil) can undergo mutations: thus, one or more of its nucleotides can be added, replaced or removed, and this randomly. In total, a few dozen lineages would exist at different scales in the world.
Interviewed by the Journal du CNRS, Bruno Lina, a researcher at the International Center for Research in Infectiology, mentions "in the jargon of virologists, we speak of variant only when mutations affect the antigenic response of the virus. Antibodies that react with the original virus no longer do so as well, if at all, with the variant.'
The Delta variant
Very contagious, the Delta variant spreads quickly, despite the acceleration of the vaccination campaign, especially since the announcements on the health pass. The efficacy of the Pfizer vaccine against the Delta variant, after one dose, is estimated at 35.6%, and after two doses, is estimated at 88%, according to data from the NEJM (New England Journal od Medicine) which estimated the risk of contracting a symptomatic form of Covid-19 in vaccinated patients, compared to unvaccinated.
The Alpha variant
Commonly known as the British variant, the Alpha variant has also been studied in the NEJM and thus, the effectiveness of the Pfizer vaccine against this variant is 47.5% after one dose and rises to 93.7% after two doses.
The South African variant
The Vidal website specifies that the protection, fourteen days after the second dose of vaccine, against any form of infection by the South African variant, amounts to 75%. The authors of a study published in the NJEM and carried out in Qatar point out that "while the effectiveness of the Pfizer vaccine on the South African variant is well below the effectiveness of the vaccine against the virus of the origin or the English variant, it nevertheless confers a very high level of protection against severe forms of infection".
The Brazilian variant
Concerning the Brazilian variant also (also called Gamma variant) mRNA vaccines have a retained but decreased efficacy. And in fact, according to an American study published by researchers in Massachusetts, mRNA vaccines are "significantly less effective" against variants, and in particular against the Brazilian strain.
Pharmaceutical companies manufacturing vaccines, such as BioNTech or Moderna, are now developing new versions of their vaccine, which will be adapted to the different variants.
1 dose: limited efficacy?
A study published in The Lancet showed that after a single dose of Pfizer vaccine against Covid-19, the body is less likely to produce protective antibodies, called neutralizing, especially against the Indian, English, and South African variants. In fact, the first dose introduces the targeted antigen into the body, while the second injection strengthens its action and prolongs the duration of the immune response. This is especially true for messenger RNA vaccines. Professor William Petri of the University of Virginia told futurasciences that "these vaccines need a booster to reactivate T cells, which in turn will stimulate antibody-producing B memory cells."
What are the side effects of the Pfizer vaccine?
When do the first side effects of the vaccine appear?
The first side effects of the vaccine may appear within a quarter of an hour after the injection and in the days that follow.
The National Agency for the Safety of Medicines (ANSM) has, on this point, indicated that "most of the adverse reactions reported during the clinical trials conducted on the BioNTech vaccine were adverse reactions of mild to moderate intensity disappearing spontaneously within a few days".
Very common symptoms
There are very common symptoms, which can be greater than one in ten cases:
- headache;
- diarrhea;
- arthralgia and myalgia;
- pain at the injection site;
- fatigue;
- chills;
- fever;
- swelling at the injection site.
Common symptoms
These symptoms occur in less than one in ten cases, but more than one in a hundred:
- nausea, vomiting;
- redness at the injection site;
Uncommon symptoms
- lymphadenopathy;
- hypersensitivity reaction;
- In addition, cases of anaphylaxis (severe allergic manifestation) have been reported.
The anaphylactic reaction should be immediately treated by intramuscular injection of epinephrine. The median interval of occurrence of this symptom is 13 minutes (between 2 and 150 minutes).
Symptoms with undetermined frequency
Other symptoms may also appear in very rare cases:
- Myocarditis;
- Pericarditis;
- Extensive swelling of a vaccinated limb;
- Swelling of the face.
Our tips to reduce and avoid possible side effects
Side effects of the Pfizer vaccine remain mild in the vast majority of cases. It is not recommended to take paracetamol as a preventive measure. The small ailments sometimes caused by vaccination are just a sign that the body's immune response is starting.
It is especially advisable to avoid drinking alcohol for three days after each injection. A study published in Nature in 2012 showed that excess alcohol can act as an immunosuppressant and affect the effectiveness of a vaccine.
What to do in case of emergency?
In case of emergency, call the UAS or go to the emergency department of the nearest hospital.
No transmission to the genome or offspring
The RNA injected via the vaccine poses no risk of transforming our genome or being transmitted to our offspring, since it does not penetrate the nucleus of cells. However, it is in this cell nucleus that our genetic material is located. In addition, under no circumstances does RNA travel to the cells of the reproductive organs.
What are the differences with other vaccines on the market?
Pfizer vs Moderna, which one to choose?
The Pfizer and Moderna vaccines have a similar mode of action: both are based on the so-called mRNA technology. In addition, their performance is very close since that of the Pfizer vaccine amounts to 95% while that of Moderna puts forward a figure of 94.1%. Their quality thus seems almost equivalent.
Pfizer or AstraZeneca?
The principles of the Pfizer and AstraZeneca vaccines, on the other hand, differ, given that the Astrazeneca vaccine uses an adenoviral vector. Indeed, the Spike protein is not expressed by means of a messenger RNA, but from an adenoviral vector, which therefore uses a recombinant chimpanzee virus. It is this adenovirus that will express the Spike protein of Sars-CoV-2. Studies estimate the performance of the Astrazeneca vaccine at 70.4% on average.
Pfizer: the differences with Janssen
The Janssen vaccine technology, unlike Pfizer, is also based on a specific adenovirus, which has been genetically modified so as not to replicate in humans and cause disease. This adenovirus is used as a vector, i.e. Transporter, of the genetic code of an antigen. Harmless parts of the virus are used as antigens and cause an immune response similar to that of the virus, but without causing a serious reaction.
According to the WHO, Janssen's vaccine has an efficacy of 85.4% against severe forms of Covid-19 as well as hospitalization related to this pathology. In addition, the results of clinical trials have indicated that one dose of the Janssen vaccine has an efficacy of 66.9% against symptomatic infection with moderate or severe SARS-CoV-2.
Differences with Sanofi
Sanofi's vaccine, called Vidprevtyn, is based on the same recombinant protein-based technology as Sanofi's flu vaccines. This recombinant protein is combined with an adjuvant (produced by GlaxoSmithKline, GSK) to stimulate the immune system.
The vaccine is currently under continuous review by the European Medicines Agency, the EMA. For the EMA, "the results suggest that the vaccine triggers the production of antibodies targeting Sars-CoV-2 and could help protect against the disease."
This vaccine is expected to be approved in the fourth quarter of 2021, subject to positive Phase III results and regulatory evaluations. Recombinant protein technology can produce very large amounts of antigens, with the proteins then injected to stimulate the immune system's response against the virus.
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