Why it is unwise to delay AstraZeneca vaccinations

A few weeks ago, an alert was reported in Austria for a grouping of two serious cases, one of which was fatal, of rare thromboembolic phenomena, coinciding with the Oxford / AstraZeneca vaccination. This motivated the preventive suspension of vaccination with a specific lot.

From that point on, other countries reported similar cases, leading to a cascade of countries that temporarily suspended vaccination (domino effect). The same thing happened in Spain. Several autonomous communities have stopped vaccination even though the authority responsible for making these decisions at the national level had not recommended it..

Finally, the Ministry of Health has taken the decision to suspend vaccination as a preventive measure. Surprisingly, it was decided despite repeated reports from the European Medicines Agency (EMA) and WHO, showing that it was more of a political decision than a technical one.

The Oxford / AstraZeneca vaccine

The AZD1222 vaccine (also known as ChAdOx1) developed by Oxford / AstraZeneca, as well as that developed by Johnson & Johnson and the Russian Sputnik V, is based on adenoviral vectors. In this case, the virus’s protein S gene is integrated into the genome of another virus, an adenovirus, which acts as a vector or vehicle to inject the gene into the nucleus of the vaccinated cell.

Adenoviruses are a type of virus that causes the common cold. These vaccines use a modified version of adenoviruses which makes them harmless: they can enter cells but are unable to replicate.

The Oxford / AstraZeneca vaccine uses a chimpanzee adenovirus (the “ChAd” in “ChAdOx1” is from Chimpanzee Adenovirus), the Johnson & Johnson vaccine uses a human adenovirus called Adenovirus 26 (Ad26), and Russian Sputnik V is the combination of two different human adenoviruses, Ad26 and adenovirus 5 (Ad5).

This type of vaccine has already been tested against other viruses such as Ebola, HIV and Zika. They are also more resistant than mRNA vaccines, DNA is not as fragile as RNA and is surrounded by the protein envelope of the adenovirus vector which protects it. For this reason, they do not need freezing temperatures for storage and they withstand refrigeration temperatures (2-8 ° C) for up to six months. Its manufacture can be easier and cheaper.

Once injected into the muscle, the adenovirus attaches itself to the surface of the cell and penetrates its interior in the form of a vesicle. Inside the cell, the adenovirus escapes from this vesicle and travels to the surface of the nuclear membrane, where it injects its DNA into the nucleus of the cell.

The adenovirus is modified so that it cannot multiply, but the SARS-CoV-2 protein S gene is recognized by the enzymatic machinery of the cell and is transcribed into mRNA. This mRNA, which carries the information of the S protein, leaves the nucleus, is recognized by the ribosomes and the S protein is synthesized, which will migrate to the surface of the cell in such a way that the vaccinated cells will expose fragments of the protein. on its surface, which will be recognized by the immune system.

90% efficiency

In addition, When these vaccinated cells are destroyed, cell debris that will contain fragments of protein S will activate a type of cell in the immune system. called antigen presenting cells.

These cells will be responsible for activating the rest of the immune cells, the T lymphocytes which regulate the response against cells infected with the virus and the B lymphocytes which will produce the antibodies against the S protein.

The Oxford / AstraZeneca vaccine requires two doses, several weeks apart. The clinical trials were published in early December. It has been tested on around 24,000 volunteers from the UK, Brazil and South Africa.

It has been shown to be effective in preventing severe cases and death from COVID-19 up to 90%. Have been described Serious side effects in 168 participants, only one of which was clearly related to the vaccine.

One of the problems with this essay is that included a small number of people over 65, which has motivated some countries to decide to use this vaccine in minors of this age, pending new clinical trials.

Phase IV pharmacovigilance

When the use of a new drug or vaccine is authorized, it begins the so-called IV phase of pharmacovigilance, a period during which the appearance of possible very rare side effects not detected during the previous phases is closely monitored.

Some serious effects are so rare that they do not become apparent until millions of people are vaccinated. As soon as a case arises, it is notified and investigated.

The cases that have occurred are thrombi in the cerebral venous sinuses. Symptoms are sudden, very severe headaches, usually affect one side of the head, may affect vision, worsen pain when lying down, do not improve, get worse over time and unresponsive not to conventional analgesic treatment. It can be fatal.

In the normal (unvaccinated) population, it is more common in women under 55 and has been associated with hormonal differences and oral contraceptives. The normal frequency is 1 to 2 cases per 100,000 people.

In Europe, around 20 million people have been vaccinated with the Oxford / AstraZeneca vaccine and 18 cases of this type of brain thrombus have been detected, the majority in patients under 55 and women.

We observe that The total number of cases recorded with similar characteristics is expected, i.e. if they had not been vaccinated a similar number of cases would have been recorded, so the EMA has supported since the early that it could be a temporary coincidence and that, evaluating the benefit-risk ratio, for the moment it was necessary to continue the vaccination.

Calm down: pharmacovigilance works

However, although the frequency is the same as in the unvaccinated population, it is worrying that it has occurred in a short period of time and, most importantly, that these cases are associated with thrombocytopenia (a decrease in platelets) which may be linked to certain dysfunctions of the immune system.

Similar effects have already been described in SARS-CoV-2 infection itself. For this reason, the EMA proposes to remain vigilant and study these cases to determine if there may be some type of causal relationship: that the cause of these effects is the vaccine, which still cannot be ruled out.

It is necessary to study in depth who, when and how they suffered from these cases, whether there is a medical history, whether they were already infected with SARS-CoV-2 without knowing it, whether they were taking other medicines (or oral contraceptives). ), do a statistical analysis, if it is an adverse immune reaction due to the vector or protein S, etc. It has been verified because there is no evidence that it is linked to specific manufacturing lots of the vaccine..

If a causal relationship between the vaccine and this side effect is confirmed, the consequences will depend on the severity and frequency. If it continues to be verified that the frequency is very low, this information will be included in the vaccine data sheet and in the vaccination alerts, and vaccination will continue if the benefit / risk ratio continues to be on the benefit side. . vaccination..

If a factor in the patient that predisposes this adverse reaction to occur is identified, this information will be included as a contraindication in the vaccine data sheet. Only if it is shown to be very common or very serious and cannot be avoided, the risk / benefit ratio may advise withdrawing the vaccine, as has happened with other medicines.

And now what?

Stopping the Oxford / AstraZeneca vaccination for several weeks (and not restarting it immediately) can have a serious effect on the course of the pandemic. It will be very difficult to quantify the number of deaths avoided by delaying vaccination.

In a time of so much uncertainty, in which there are concerns about the spread of new variants of the more transmissible, and perhaps more deadly, virus, in which we are already talking about the fourth wave, in which there is a shortage vaccine, in which we need to vaccinate as many people as possible as possible, delaying vaccination is unwise.

Is question of benefit-risk assessment: the risk of dying or becoming ill from the coronavirus and that the chaos in which we are plunged will continue is still much greater than the possible benefit of suspending vaccination as a precaution.

To this must be added the effect on the role of the EMA. What good is this agency if governments (even regional governments) decide to make their own decisions despite its recommendations? What is EMA used for?

Finally, how does all of this affect confidence in vaccines?

The author is professor of microbiology, University of Navarre

KEEP READING: