The first vaccines approved in Europe against COVID-19 — Pfizer / BioNTech, Moderna, Astrazeneca / U. Oxford and Janssen – are also the first of their kind: there is hardly any precedent for others made with the same technology. They are vaccines made of nucleic acids, the molecules DNA or RNA. In this infographic its operation and differences are explained in a basic way.

Unlike traditional vaccines, they do not contain any live microorganisms – or fragments of them – so there is no chance that they will cause the disease they are intended to prevent.

However, these new vaccines have raised another fear: that the DNA or RNA they contain will somehow interfere with the DNA of the vaccinated person. Experts are unanimous in stating that this risk is non-existent.

DNA, RNA and proteins

DNA is the molecule that genes are made of, and genes hold the information necessary to build the tens of thousands of different proteins that operate in living things. Each organism’s DNA is unique and is present in all its cells. In humans it is in the nucleus of every cell.

The already approved vaccines contain copies of part of the DNA or RNA of the coronavirus, specifically of the region that orders to manufacture the protein with which the virus enters human cells

As for RNA, its function – stated in very basic terms – is to take the information from the DNA out of the nucleus of the cell, and have it translated into proteins. This process of translation from RNA to protein occurs in the cellular environment outside the nucleus, the so-called cytoplasm of the cell.

DNA and RNA molecules can be chemically constructed in the laboratory. The already approved vaccines against COVID-19 are RNA – those from Pfizer / BioNTtech and Moderna – or DNA – those from AstraZeneca and Janssen. They contain laboratory-made copies of part of the SARS-CoV-2 coronavirus DNA or RNA; specifically of the region that orders to manufacture the S protein, the one that the virus uses as a key to enter human cells.

Works!

When someone is vaccinated, their cells begin to produce the virus’s protein S. Your immune system detects it, notices that it is foreign, and produces defenses against it.

One of the great good news since the start of the pandemic is that this does indeed happen. It was not at all obvious. Although the idea of ​​making nucleic acid vaccines was raised as early as the 1990s, its development has had to overcome major obstacles. So much so that the Pfizer / BioNTech and Moderna vaccines are the first RNA vaccines ever used, and in the case of the DNA ones – AstraZeneca and Janssen – there is only one precedent for humans, the Ebola vaccine, approved in 2020.

Nucleic acid vaccines are produced faster than traditional ones, and their formulation is relatively easy to adapt to possible mutations of the virus

Why, being a technology not used before, in the pandemic are companies that have opted for it? One reason is that it is a well-studied technology. In recent decades, research groups around the world have generated abundant evidence that the chances of success were reasonable.

But there are more reasons. Nucleic acid vaccines are produced faster than traditional vaccines, and their formulation is relatively easy to adapt to possible mutations in the virus.

They are also theoretically safer vaccines. Classic vaccines contain the weakened virus or fragments of it. As the virus is attenuated it should not cause disease, but there is always a small risk. In DNA and RNA vaccines this possibility does not exist.

There is also no risk of interaction between the DNA or RNA of the vaccine and the DNA of the person who receives it.

Chocolate dragees

We first analyze the case of RNA vaccines, composed of this molecule wrapped in a tiny capsule of fat –Margaret Liu, a pioneer in this type of vaccine, has compared them to a sugar-coated chocolate (RNA) dragee (fat) -. This RNA enters human cells, but not their nucleus, where the DNA of the vaccinated person is.

The RNA of the Pfizer / BioNTech and Moderna vaccines does not access the nucleus of human cells, where the DNA of the vaccinated person is

When the vaccine is injected, macrophages – a type of defensive cell – near the puncture site ingest the fat-encased RNA. The cellular machinery in the macrophage cytoplasm will translate the RNA information into proteins, so that now these cells can produce the virus S protein and place it on their outer membrane, to display it outside.

This “induces in the body a defensive response such as the one that would be generated to protect us from a natural SARS-CoV-2 infection,” he explains on the website of the New England Journal of Medicine (NEJM). Paul sax, an infectious disease expert at Harvard Medical School.

“Then the cellular enzymes degrade the RNA that has been introduced with the vaccine. No live virus is involved in the process, and no genetic material enters the nucleus of the human cell. Although these are the first RNA vaccines to be used in the clinic, scientists have been working on them for years, ”Sax adds.

Virus like a Lego truck

The AstraZeneca vaccine is a human-safe chimpanzee cold virus to which SARS-CoV-2 protein S DNA has been added. In this case, when a person receives the vaccine, this DNA does enter the nucleus of their cells, “but at no time does it integrate with human DNA,” he explains. Santiago Elena, CSIC researcher at the Institute of Integrative Systems Biology (CSIC-UV).

Vaccine DNA disintegrates and clears cells in just a few days, but the human immune system continues to build defenses against the coronavirus

“What happens when the vaccine’s DNA enters the nucleus is that the nuclear machinery recognizes it and starts to transcribe it into RNA,” adds Elena. “It is the same process of the attenuated virus vaccines that have been used since the 18th century against smallpox: the vaccine virus uses the nuclear machinery to generate the messenger RNA and, from this, already in the cytoplasm, its proteins , but it does not interact with human DNA ”.

In reality, the vaccine virus is a set of genetic orders that researchers have assembled one by one in the laboratory, knowing what each one does: “The virus is genetically modified, so that it has only the instructions we want. It’s like building a truck with Lego: if you want, you can put a trailer on it with more or fewer pieces, if you don’t just leave the tractor unit… We control what we want it to do ”, says Elena.

After a few days the DNA of the vaccine disintegrates and eliminates from the cells, but the human immune system will have already seen the protein S of the coronavirus and will be generating defenses against it.

This article was originally published on Expert voices, a section coordinated by SINC on the website of the Spanish vaccination strategy vaccinacovid.gob.es.



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