The Astrazeneca vaccine has made a fuss. According to a recent study from the European Medicines Agency (EMA), which has its headquarters in Amsterdam, the Astrazeneca vaccine is strongly suspected of having potentially fatal blood clot side effects.

Shortly thereafter,  the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) disclosed that it may have found evidence of a connection between blood clot cases and the Astrazeneca-Oxford vaccine. The EMA and MHRA reports immediately sparked concern in the European region.

Eleven countries in Europe instantly suspended the use of the Astrazeneca vaccine, followed by Thailand. In Indonesia there have been no cases of blood clots due to the vaccine, but, pending further studies, the Minister of Health, Budi Gunadi Sadikin, announced the suspension of the use of Astrazeneca vaccine (15/3/2021).

So far, the findings of the side effects of blood clots did occur in European region. Until the end of March 2021, there were 79 people who experienced side effects of blood clots and 19 of them died between the ages of 18-79 years. However, EMA Executive Director, Emer Cooke, explained that the benefits of the vaccine still far outweigh the risks of the side effects.

So far, the virus that causes Covid-19 has infected 135 million people and caused 2.91 million deaths globally, so the 79 cases of blood clots side effects that are temporarily suspected to be caused by Astrazeneca vaccine represent a very small percentage compared to the overall vaccine recipients, which has reached about 200 million people.

Some countries responded to the case more moderately, for example, by imposing certain age limits and conditions for Astrazeneca vaccine recipients. This side effect of blood clots is very important to be studied further, although its percentage at global level is not alarming.

This case shows that a vaccine that is designed and produced quickly, of high quality in an emergency situation, still has rudimentary potential. However, health authorities in various countries are also quick to act: they observe, find cases, and immediately take mitigation steps.

Haram vaccine controversy

This blood clotting effect was not the only case of Astrazeneca. In Indonesia, whose population until March 8, 2021 had received 1.1 million doses of Astrazeneca, there were other cases. Not long ago, the Indonesian Council of Ulama (Majelis Ulama Indonesia, MUI) had made a headline by declaring that the Astrazeneca vaccine was haram. Despite being haram, the vaccine produced by SK Bioscience, Andong, South Korea, can be used because the situation is in a pandemic emergency.

This statement was announced by the Head of the MUI Fatwa Division, Asrorun Ni'am Sholeh, on March 19, 2021. The basis for the MUI statement was that because the vaccine production process utilized trypsin produced from swine pancreas.

Of course, the MUI declaration immediately sparked pros and cons. However, the East Java Provincial MUI did not agree with the central MUI statement. The chairman of the East Java MUI, M. Hasan Mutawakkil Allah, stated that the vaccine developed by the University of Oxford and Astrazeneca was halal. Not only halal, but also thayban (good). Kiai Hasan and many religious leaders in East Java even received the injection of the Astrazeneca vaccine in an open event covered by media.

The polemic of haram vaccines had also hit other countries. In India, the Secretary General of Raza Academy, Saeed Noorie, was concerned that the vaccine was produced using swine gelatin. “There are reports of Chinese vaccines using swine body parts. Since swine is haram for Muslims, vaccines containing swine body parts are not allowed," said Saeed as quoted by About Islam, December 2020.

The United Arab Emirates is different. The UAE Fatwa Council declared the corona vaccine, even if it contains swine body parts, is halal for Muslims, based on a report in the Free Press Journal, December 2020.

So, the stand of the central MUI that Astrazeneca vaccine was haram (even though it was allowed), was actually understandable because the same thing also happened in other countries, as did the statement of East Java MUI that the vaccine was halal. Fatwa is not always a single opinion because fatwa takes the point of view of religious arguments considered as the strongest by each mufti (the fatwa provider) by also practicing wisdom in regard with the presence of emergency situation.

So, what was the basis of East Java MUI so that it dared to take a different stand with central MUI? Was it true that this vaccine contained swine trypsin and what was the medical explanation? Let's discuss it from a scientific point of view.

Trypsin only detaches cells

Trypsin is an enzyme that is daily present in human body and is secreted by the pancreas. Trypsin functions to break down protein so that protein can be absorbed by the intestine in the digestive process. In its development, trypsin, a protease protein, can be used in tissue culture technology (mass and rapid cell culture technology). However, the trypsin used in this tissue culture technology does not come from humans, but mostly from swines (porcine trypsin).

The enzyme is used as a reagent (a reactant, which causes two substances to react chemically), in this case as a separator between cells. This is what happened in the manufacture of the Astrazeneca vaccine using tissue culture technology.

The genetic engineering of SARS-CoV-2 virus using the genetic code of the corona virus is a very advanced bio-engineering technology. The corona virus vaccine developed by Astrazeneca does not work by sending the entire virus, but only sends the genetic command code (the spike) into human cells to build viral proteins that are carried by adenoviruses as messengers and are expected to stimulate the immune system to make antibodies and increase its defense against the corona virus.

So, this Astrazeneca vaccine uses genetic engineering known as DNA vaccine, which uses adenovirus as its vector or messenger. Adenovirus is the virus that causes us to catch common cold. However, due to effectiveness consideration, Astrazeneca used the chimpanzee adenovirus as a messenger (carrier) for the genetic code of the corona virus.

The process of making the combined virus begins by inserting the genetic code of the corona virus that encodes the spike protein (S) into the DNA of the adenovirus. This DNA (deoxyribonucleic acid) can be called a generic blueprint. Then, this mixed DNA is inserted into the media containing the cell culture. It is like we spread mung bean seeds onto media in the form of tissue or wet soil, so that they can germinate.

In this case, the cell culture medium used by Astrazeneca is called T-REx-293, a derivative of HEK293 (Human Embryonic Kidney 293) cell line derived from human embryonic kidney cell culture. However, in the process, this T-REx-293 can grow if attached to a culture bottle. Thus, the cells are grown by attaching to the culture bottle.

To harvest them, the cells must be detached from the culture bottle, just as we harvest oyster mushrooms growing in media bottles or other mushrooms growing attached to trees. In mushrooms, we just cut it. However, in this T-REX-239, to detach it from the culture bottle, we have to drip it with the enzyme trypsin. Thus, the function of trypsin is to release T-REX-239 which is attached to the culture vial. This release process is called trypsinization.

The trypsinization process begins by heating trypsin to a temperature of 37 degrees Celsius. The media bottle containing the cell cultures and their nutrients will be cleaned until only the cell cultures remain attached to the walls of the agar bottles. So that the cells do not die from drought, the bottle is put in a solution containing sodium salt, the solution is discarded.

Trypsin is then put into the bottle to start releasing the cells attached to the bottle. This process is quite short, about 30 seconds to 5 minutes. Furthermore, trypsin was neutralized with a solution containing Fetal Bovine Serum (FBS) in an amount of 4-5 times more than trypsin. Thus, the cultured cells can be taken alive and clean of trypsin.

Thus, the function of trypsin is limited to removing cells (which already contain the vaccine candidate adenovirus) attached to the culture bottles. Trypsin is by no means a building block for vaccines, and the vaccine does not contain any trypsin at all.

The trypsin was destroyed by the FBS solution and nothing was left in the culture medium. If the trypsin still lasts more than 10 minutes because the FBS solution has not been destroyed, the cultured cells die and are destroyed, the process fails because the trypsin will destroy the cell wall.

This is why the process of trypsinization or removal of cells from their walls must take place quickly. Once the cell is detached from the wall, trypsin must be removed immediately. This is a zero sum game. If trypsin is still present or alive, the cell will die. On the other hand, if the cell is still alive, it means that the trypsin is destroyed and disappears. Thus, according to medical rules, the results of cell culture that already contained adenovirus, and later became the Astrazeneca vaccine, did not contain swine trypsin at all.

The use of enzymes or materials derived from animals has the potential to carry a risk of contamination from hazardous and infectious substances. For example, in 2010, the use of trypsin enzymes from swine in the production of Rotavirus vaccines demonstrated the presence of DNA sequences of porcine circovirus viruses from swine. From this experience, the use of traditional trypsin, which is mainly extracted from the pancreas of swine or cattle, should be replaced by recombinant (mixed or combined) trypsin models.

Trypsin-EDTA used in HEK293 cell culture is known to be very effective in removing adhering cells from the media completely, in a short time, and at a relatively low cost, despite the potential risk of contamination.

Astrazeneca Indonesia has clarified that it does not use animal-based ingredients. Even so, this clarification still raises questions, for example, is the process of making the Astrazeneca vaccine used a trypsin enzyme that is different from the T-REx-293 culture guidelines? Further clarification is needed, even though it has been medically explained that the Aztrazeneca vaccine does not contain swine.

Apart from the question of blood clots and the accusation of haram vaccines described above, let's make the Covid-19 vaccination a success. Vaccination is a method that has proven its reliability since a century ago, and this is our endeavor to overcome the pandemic while still adhering to health protocols. Vaccination has proven to be far greater than the risk of exposure from not being vaccinated. 

Djoko Santoso
Professor, Faculty of Medicine, Universitas Airlangga
Chairman of Health Department, Indonesian Council of Ulama, East Java

Translated from Indonesian:
"Pembekuan Darah dan Tudingan Vaksin Haram"
by Djoko Santoso
Media Indonesia, 12 April 2021
Source: https://mediaindonesia.com/opini/397259/pembekuan-darah-dan-tudingan-vaksin-haram