AstraZeneca: origin of the vaccine, efficacy and cases of thrombosis

This vaccine, named Vaxzevria, was developed in 2020 in partnership with the University of Oxford. Its principle is based on a technology using an adenovirus to express the Spike protein in the body: it is thus a viral vector, which is a harmless and attenuated (weakened) virus that has been modified in order to transmit genetic instructions. to the cells of the body. It obtained its marketing authorization (AMM) in Europe on January 29, 2021.

 Context of the Covid-19 vaccination

In the context of the global Covid-19 pandemic, caused by the SARS-CoV-2 coronavirus, the AstraZeneca laboratory, a pharmaceutical group of British and Swedish origin, has produced a vaccine against this respiratory infection which is the cause of more than 4 , 5 million deaths worldwide.

A dispute opposed the European Union to the firm AstraZeneca and concerned delays in vaccine deliveries: it ended on September 3, 2021. Indeed, by the end of the first quarter of 2022, the Anglo-Swedish group will therefore deliver 200 million doses to the EU in stages. This will complement the 100 million doses that had already been received by Member States as of June 30, 2021.

 What is the principle of the Astrazeneca vaccine?

The Vaxzevria , name of vaccine produced by AstraZeneca, consists of a live viral vector non-replicative, based chimpanzee adenovirus. This vaccine is also called Oxford AZD1222, ChAdOx1-S, or Covid-19 Vaccine AstraZeneca.

As the CNRS Journal explains, the principle of vaccination is always the same, since it involves presenting a modified pathogen to our immune system in order for it to learn to recognize it. Thus, the organism will manufacture specific antibodies, and these will be ready, in the event of a natural encounter with the pathogen, to neutralize it.

In fact, it is not the pathogen as such that triggers the immune response, but the antigens, which are specific proteins located on the surface of the virus.

Operation and principle of action

The best recognized antigen of SARS-CoV-2 is the S protein, known as Spike: this spike-shaped protein gives the virus its spiky appearance. The idea of ​​a vaccine being to inoculate the pathogen in a completely harmless form, several technologies are possible, among which, viral vectors.

It is this principle which is used by the vaccine produced by AstraZeneca, and which consists in using a real virus, in this case a modified chimpanzee adenovirus. Indeed, the RNA of this adenovirus is modified and the code of the Spike protein is integrated therein. You should know that the viral vectors used in vaccines have no effect on the DNA of the organism and do not interact with it.

Here are more concretely the different stages of the action of a vaccine based on a viral vector:

  • the viral vector vaccine uses a version of an attenuated virus (weakened so that it is no longer pathogenic but still capable of replicating in the human body) which will give instructions, in the form of a genetic code, to the cells of the organism;
  • after the injection, the Adenovirus carrying the instructions for the creation of the Spike proteins enters the cells;
  • the body creates spike proteins;
  • the immune system detects these foreign proteins and produces antibodies and immune cells capable of attacking them;
  • the body quickly eliminates adenovirus as well as genetic information;
  • if the vaccinated individual is subsequently infected with the coronavirus, their immune system will detect the Spike protein and destroy the virus.

The viral vector vaccine method is effective, but it is complex.

Composition

A 0.5 ml dose of vaccine contains an antigen, i.e. at least 2.5 X 10 8  chimpanzee adenovirus viral particles, encoding the Spike protein of SARS-CoV-2. This vaccine is produced in cells called HEK for Human Embryonic Kidney, or genetically modified human embryonic kidney cells, and by recombinant DNA technology.

This dose also contains excipients, listed below:

  • L-Histidine;
  • L-Histidine hydrochloride monohydrate;
  • Magnesium chloride hexahydrate;
  • Polysorbate 80 (E433);
  • Ethanol (about 2 mg in a dose);
  • Sucrose;
  • Sodium chloride;
  • Disodium edetate (dihydrate);
  • Water for injection.

 Who can receive the AstraZeneca vaccine?

The injection of the vaccine is intramuscular, it is preferably carried out in the deltoid muscle.

Children over 12 and adults?

In children and adolescents under 18 years of age, vaccination with Astrazeneca is not yet effective, as the safety and efficacy of this Vaxzevria vaccine in the pediatric population has not yet been established. .

This vaccine has also been suspended for adults under the age of 55, who should preferentially receive the Pfizer vaccine or that of Moderna.

Seniors and over 55

Indeed, according to an opinion issued by the HAS on March 19, 2021, it is recommended to administer the vaccine from the age of 55, because of the existence of a link between the occurrence of rare forms and severe thrombosis with thrombocytopenia and vaccination with the AstraZeneca vaccine.

No dosage adjustment is necessary in the elderly population.

Pregnant women

Vaccination with AstraZeneca vaccine during pregnancy should be considered only if the potential benefits outweigh the potential risks to the mother and fetus.

Currently, and since an opinion issued on March 1, 2021, the HAS recommends favoring, in pregnant women, mRNA vaccines, either those from Pfizer or Moderna.

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People with co-morbidities

Vaccination is recommended for people with co-morbidities. Indeed, these increase the risk of developing a severe form of Covid-19. These co-morbidities are, mainly, obesity, cardiovascular diseases, respiratory diseases and diabetes.

For the WHO, “vaccines against Covid-19 are safe for most people aged 18 and over, including those with already existing conditions of any kind, including autoimmune diseases. -immunes “.

 Are there any precautions for use and contraindications?

Prevention

Since hypersensitivity has been reported, it is essential to monitor the vaccinated subject in the event of an anaphylactic reaction following administration of the vaccine. There is also a need for appropriate medical treatment. Close monitoring is recommended within 15 minutes of vaccination.

In addition, a second dose of AstraZeneca vaccine should not be given in people who have experienced an anaphylactic reaction following the first dose.

Contraindications

  •  The capillary leak syndrome corresponds to a new contraindication (as of July 1, 2021).

According to Decree No. 2021-1059 of August 7, 2021, here are the cases of medical contraindication preventing vaccination against Covid-19. They allow the issuance of the certificate of contraindication, and thus, to derogate from the vaccination obligation.

The contraindications listed in the product characteristics are as follows:

  • a documented history of allergy, with the advice of an allergist, to one of the components of the vaccine, in particular to polyethylene glycols and by risk of cross-allergy to polysorbates;
  • an anaphylactic reaction of at least grade 2 (i.e. damage to at least two organs) following a first injection of a vaccine against Covid, performed with the expertise of an allergist;
  • in people who have already had episodes of capillary leak syndrome (contraindication common to Vaxzevria vaccine and Janssen vaccine);

Medical recommendation not to initiate a vaccination (first dose):

  • Pediatric multisystem inflammatory syndrome (PIMS) post Covid-19. Indeed, although Covid-19 affects the vast majority of adults, in children, a multisystem inflammatory syndrome has been observed, in the context of SARS-CoV-2 infection. Called PIMS, this syndrome is a rare condition. However, it is serious, requiring to be detected early in order to initiate hospital treatment. 520 cases were identified in France on June 13, 2021, including one death, and two thirds of the children were hospitalized in intensive care. The suggestive symptoms are not very specific: association of fever, a deterioration of the general state and digestive disorders. Other clinical signs may also be present, such as neurological or respiratory signs.

A recommendation established after multidisciplinary medical consultation indicates not to perform the second dose of vaccine following the occurrence of an adverse effect of severe or serious intensity attributed to the first dose of vaccine.

Finally, a final contraindication to the AstraZeneca vaccine and to vaccination against Covid-19 in general is treatment with anti-SARS-CoV-2 monoclonal antibodies, as well as myocarditis or pericarditis prior to vaccination and still evolving.

 What is the dose of AstraZeneca vaccine?

What is the recommended duration between the two injections?

The WHO indicates that the recommended dosage is two doses, administered intramuscularly. Each dose contains 0.5 ml, and they should be injected with an interval of eight to twelve weeks.

While the MA for the AstraZeneca vaccine provides for a delay of four to twelve weeks, in fact, efficacy and immunogenicity data show the positive impact of the lengthening of the duration and the persistence up to twelve weeks of protection. conferred by the first dose: hence the recommendation of the HAS, in France, to favor an interval of nine to twelve weeks between the two doses.

Should you be vaccinated when you have had the Covid?

Based on work by the SPILF, the French-speaking Society for Infectious Pathology, the HAS recommendations on the vaccination of people who have contracted Covid-19 (confirmed by an RT-PCR or positive antigen test) indicate that these people should carry out the vaccination within a period of almost six months, and not before a period of at least three months after infection. Only one dose is needed for these people.

In addition, a case-control study published in the journal of the US CDC of August 6, 2021 that was conducted in May-June 2021 in Kentucky included 246 cases of people with a history of infection and with a new proven infection and 492 controls. , people with a history of infection, without new infection.

Results: among people previously infected with SARS-CoV-2 in 2020, the frequency of re-infections is lower in those vaccinated.

Third booster dose: why is it recommended?

Eighteen million French people are affected by this recall, or a third vaccine dose, from September. This third dose is recommended to compensate for the gradual decrease in the effectiveness of vaccines against Covid-19.

Thus, from September, those over 65 and the French with co-morbidities will be able to receive a third dose of vaccine. Regardless of the doses that have been previously injected, this third dose will be an mRNA vaccine, either from Pfizer or Moderna.

Indeed, the HAS recommends, in an opinion delivered on August 27, 2021, to vaccinate with mRNA vaccines. This booster dose is recommended at least six months after the primary vaccination, and three months after for immunocompromised people.

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How is AstraZeneca vaccine stored?

AstraZeneca vaccine can be stored at 2 to 8 ° C.

 Is the Astrazeneca vaccine effective?

Protection against covid-19

The ANSM (National Medicines Safety Agency) website indicates that clinical trials conducted on 24,000 participants have demonstrated about 60% efficacy of the AstraZeneca vaccine. The duration of protection conferred by this vaccine against Adenovirus has not been established and is currently still under evaluation. Regarding viral transmission or shedding, the impact of the AstraZeneca vaccine is not yet known because the data are still insufficient.

In fact, with respect to protection, data from the UK’s Commission on Human Medicines suggests that a single dose would provide 70% protection after 21 days, and a second dose would increase the effectiveness of the drug. vaccine if given 12 weeks after the first dose, increasing the level of protection to about 80%.

Protection against variants

According to a study conducted by Public Health England on 19,000 patients, which was published on July 21, 2021, two doses of AstraZeneca vaccines protect against the symptoms of the Alpha and Delta variants of covid-19 at comparable rates.

The duration of protection and the reduction of transmission are not yet established for variants.

Delta variant

Scientists believe that the Delta variant is more contagious than previous variants of Covid-19. The results of the study conducted by Public Health England indicate that two doses of the AstraZeneca vaccine are 67% effective against symptomatic forms of the Delta variant. Efficacy drops if the patient has received a single dose.

Alpha variant

In addition, this English study also specifies that two doses of the AstraZeneca vaccine are 74.5% effective against the symptomatic forms of the Alpha variant. Likewise, the efficacy drops in the event that the patient has received only one dose.

South African variant

“There is currently a doubt about the efficacy of the AstraZeneca vaccine against the variant that has emerged in South Africa”, indicates the orientation council of the vaccine strategy in France.

A study conducted at the University of Johannesburg and published on February 7, 2021 estimates that the AstraZeneca vaccine “offers minimal protection against mild to moderate infection” by the South African variant, exhibiting an average efficacy of 22% against these forms moderate.

However, the AstraZeneca vaccine remains more effective against the severe forms caused by this South African variant. In fact, it would be the messenger RNA vaccines, namely those from Pfizer and Moderna, which would retain their efficacy the most against the South African variant, despite a sharp drop in efficacy in their case as well.

Brazilian variant

At the moment, there are still few data regarding the protection of the AstraZeneca vaccine against the Brazilian variant. The impact of vaccination against this variant is under study, but recent studies seem to indicate an attenuated efficacy of vaccination for this variant.

1 dose: limited effectiveness?

A single dose of vaccine has limited efficacy.

This is because when an individual’s immune system first encounters a vaccine, it activates two types of white blood cells:

  • on the one hand, the B lymphocytes, at the origin of the production of antibodies. But this type of cell has a limited lifespan, and without the second injection, the decline in antibodies present in the body is rapid (this type of antibody response is called “humoral immunity”);
  • on the other hand, T lymphocytes, cells adapted to identify a particular pathogen and kill it (this is called “cellular immunity”). A second dose allows memory cells that have already been accumulated to differentiate and proliferate.

In fact, a second dose is a new exposure to the antigen, which will “also allow the immune system to select the types of antibodies which have the most affinity with this foreign element. They will then be able to fight it even more effectively. if it reappears in the future “,

What are the side effects of the AstraZeneca vaccine?

The overall safety of Vaxzevria is based on data from four clinical trials conducted in the UK, Brazil, and South Africa. This observation was made in a total of 24,244 participants aged 18 and over.

When do the first side effects of the vaccine appear?

The first side effects are usually present during the first 24 hours after vaccination and go away quickly, for the great majority.

Frequent symptoms

In this group of 24,444 people, the side effects observed were:

  • tenderness at the injection site (63.8%);
  • pain at the injection site (54.30%);
  • headache (52.7%);
  • fatigue (53%);
  • myalgia (43.9%);
  • malaise (44.4%);
  • a fever ;
  • chills ;
  • arthralgia;
  • nausea.

The vast majority of these side effects are mild to moderate in intensity. In fact, they usually resolved within a few days after vaccination.

Symptoms of unknown frequency 

More generally, here are the undesirable effects, with undetermined frequency, which have been noted. It’s about :

  • blood and lymphatic system disorders: either, quite frequently, thrombocytopenia, which is a drop in the number of blood platelets, and infrequently lymphadenopathy, i.e. enlargement of one or more lymph nodes . In fact, the mild thrombocytopenia frequently reported in clinical trials has been shown to be transient;
  • immune system disorders: at an unknown frequency may develop anaphylaxis or hypersensitivity;
  • metabolic and nutritional disorders: infrequently, a decrease in appetite may appear;
  • disorders of the nervous system: as already mentioned, headaches are very frequent, and it may also occur, infrequently, dizziness, drowsiness or lethargy;
  • vascular disorders: very rare, thrombotic thrombocypenic syndrome has been reported. Thus, after the vaccine has been marketed, severe and very rare cases of thrombosis (blood clot forming in an artery or vein) have been reported. Still in terms of vascular diseases, it can also occur, at an unknown frequency, a capillary leak syndrome, characterized therefore by episodes of loss of fluid in extravascular tissues;
  • gastrointestinal complaints: nausea has been mentioned, in addition, vomiting and diarrhea can occur frequently, and abdominal pain infrequently;
  • skin and subcutaneous tissue disorders: uncommonly hyperhidrosis, pruritus, rash, urticaria, and angioedema may occur;
  • musculoskeletal and connective tissue disorders: arthralgia and myalgia, as in clinical trials, are very common in the population vaccinated with AstraZeneca, in addition, pain in the extremities may occur frequently;
  • general disorders and abnormalities at the administration site: very frequently, tenderness, pain, heat, pruritus or bruising at the injection site may appear, but also fatigue, malaise, feverishness , chills. Finally, swelling or erythema at the injection site, fever (measured at over 38 ° C), flu-like illness or asthenia frequently appear.
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Another side effect observed in rare cases: Guillain-Barré syndrome

The European Medicines Agency, the EMA, has recorded 156 cases of Guillain-Barré syndrome in patients who have been vaccinated with the AstraZeneca vaccine. So there may be an unwanted effect of this vaccine.

What is Guillain-Barré syndrome?

Guillain-Barré syndrome is a rare condition, in which the patient’s immune system attacks peripheral nerves. It is characterized by weakness linked to the slowing down of nerve transmission, or even progressive paralysis. The WHO site recalls, however, that “most people with Guillain Barré syndrome recover fully, even in the most serious cases”.

Focus on cases of thrombosis

A temporary suspension of the AstraZeneca vaccine was pronounced in March 2021, due to the occurrence of cases of thrombosis, before it could be used again after a few days and a positive opinion from the European Medicines Agency .

Director of the Institut Pasteur in Lille, Xavier Nassif then expressed himself: “To link an event which can be an epiphenomenon, linked to anything else, to the injection of a vaccine seems to me extremely complicated and detrimental”.

Finally, the European Medicines Agency confirmed the benefits of this vaccine, which are much “greater than its risks”. The drug agency (ANSM) for its part confirmed on March 26, 2021 the existence of a risk, described as “very rare”, of atypical thrombosis associated with the AstraZeneca vaccine. The authorities stress that the risk-benefit balance in the face of the epidemic remains “positive”. However, rapid specialist medical care must be taken in the event of atypical thrombosis.

Our advice to reduce and avoid possible side effects

It is not recommended to take alcohol within three days of vaccination. Taking paracetamol to prevent symptoms is not recommended. On the other hand, in case of headaches or pain, taking paracetamol is recommended.

What to do in an emergency ?

In case of emergency, you must call the Samu (15) or go to an emergency department of a hospital center.

 What are the differences with other vaccines on the market?

Astrazeneca vs Pfizer, which one to choose?

The Pfizer vaccine has shown a higher percentage of protection in clinical trials than the Astrazeneca vaccine. The principles of these two vaccines are different, since Pfizer’s vaccine is a messenger RNA vaccine. This technology is recent, and very promising.

However, this is the first time that it has been used on a large scale in the population, when AstraZeneca’s vaccine technology is based on viral vectors. These are a promising alternative to conventional vaccine platforms.

In addition, technology based on viral vectors has already been used on a large scale for decades: in gene therapy, in cancer treatments, in animal vaccination. It has also recently made it possible to produce two vaccines against Ebola virus disease in humans.

AstraZeneca or Moderna?

Like Pfizer, Moderna is a messenger RNA vaccine, and its percentage of protection is higher than the AstraZeneca vaccine. 

Astrazeneca differences with Janssen

Astrazeneca and Janssen’s vaccines are both based on the same principle, that of a viral vector. However, there is a notable difference since the Janssen vaccine only requires one injection while the Astrazeneca vaccine requires two.

Differences with Sanofi

The principle of these two vaccines is different. Thus, the vaccine which should soon be produced by Sanofi (during the fourth quarter of 2021) is based on recombinant protein technology.

This consists in causing the Spike protein to be produced in large quantities by cultured human cells infected with a baculovirus to which the gene encoding the Spike protein has been added.

It is therefore still an innovative vaccine strategy full of promise. This recombinant protein technology has been proven: Sanofi is already using it in vaccination against seasonal influenza.