November 28, 2020

Genetically Engineered Coronaviruses: A Possible Vaccine



The news about the SARS-CoV-2 coronavirus is happening at breakneck speed and the information from one day is mixed with the one from the day before. It is difficult to keep track of progress, especially when, in a matter of a week, most of the data we handle will be out of date. It may seem like a maddening scenario in which, as Lewis Carroll wrote: “To stay where you are, you have to run as fast as you can, and if you want to go somewhere else, you must run at least twice as fast.”

However, this is the day-to-day life of most scientists, who, in order not to be out of date, need to study the dozens of articles of their discipline that are published each month. Through the headlines, we accompany thousands of scientists who are facing a new and unexplored problem. Not long ago we did not even know about the existence of SARS-CoV-2 and in just three months we already have mountains of data on it. Scientists from all over the world have joined in a common undertaking, a time trial account to meet the enemy and thus be able to build the weapon that protects us from him.

Before vaccines

During these months many research centers around the world have decided to undertake finding a vaccine. A drug makes us immune to SARS-CoV-2. When our immune system faces an invader for the first time, be it a virus, bacteria, fungus or parasite, it does not “know” how to attack it, so it takes generic, but ineffective, measures, as if it were blind. However, as innate immunity cells, like macrophages, fight, they take fragments of the enemy and display them on their surface, like trophies. This is not a macabre ritual, but the first step in developing a much more powerful immune response. Other different cells, such as lymphocytes, will “analyze” the dismembered fragments of the enemy and thanks to this, they will produce antibodies capable of recognizing the invader and thus attacking it.

The descendants of these cells of acquired immunity will maintain their new ability, and if they detected the same enemy again, they would recognize it immediately, triggering a much more powerful and effective immune response than the first time. This is why some diseases, like measles, we only have once. And, although it is true that there are viruses against which we are unable to develop a specific immune response, those of the coronavirus family have not behaved like this on other occasions and nothing makes us think that SARS-CoV-2 is an exception. The cases of COVID-19 patients who return positive after discharge can be justified by impressions in the diagnostic test (false negatives) or understood as exceptional cases where a specific failure of the immune system fails to develop immunity. Another explanation would be that the virus had mutated into a strain distinct enough that the lymphocytes could no longer recognize it, but the coronavirus mutates less than other RNA viruses, like the flu, for example, and an accelerated production of strains is not expected (or has been detected).

Vaccines there are more than one

What vaccines are trying to do is simulate this natural immunization process, exposing you to the viruses or bacteria against which we want to generate immunity. However, it is not as easy as it sounds. To prevent the vaccine from causing an infection, the pathogens it contains must be dead or “in poor shape.” Inactivated vaccines, for example, neutralize viruses, making it impossible for the disease to develop. So the flu shot cannot make the flu. However, there are more effective ones, such as attenuated vaccines. In them, the virus is so weakened that a healthy immune system will be able to easily defeat you. The problem is that they cannot be administered to immunocompromised people and they need conservation conditions that cannot be guaranteed worldwide. It is possible that in the fight against SARS-CoV-19 we need something more powerful than inactivated vaccines and more universal than attenuated vaccines. But luckily, since it was invented by Edward Jenner and popularized on the Balmis Expedition, vaccines have come a long way. Cow pustule scrapings have disappeared and have been taken over by the most advanced biotechnology.

Some virologists consider that the best way to prevent SARS-CoV-2 in the long term will be a recombinant vaccine. These seek to inject the pathogen fully alive, without attenuation, although with a slight change. The same virus that produces the disease would not be inoculated, but one modified to eliminate its ability to reproduce and harm our cells. To understand it, we have to understand that the genetic information of some viruses, and among them the coronavirus family, is not made up of a DNA molecule like ours.

How to produce a recombinant vaccine?

Its genome is in the form of RNA, a similar molecule, but it normally has a single chain of information, instead of the two that are intertwined in the classic DNA image. This string has a kind of text on how to build the virus, but encoded with only four letters. In total there are 30,000 characters, a sequence of adenine (A), cytosine (C), guanine (G) and uracil (U). The scientists’ mission is to find which fragments, such as the ORF8 region, hold the relevant information to build the virus’s exterior. In summary, the genes that encode the proteins that coat the virus to give them to our immune cells in a tray so that they can display them on their surface.

Once the RNA sequence that stores this information is isolated, it will have to be converted into DNA. The format change involves replacing the uracil with thymine (T) and the lonely chain will have to join another that complements it letter by letter following a simple rule: each A is joined to a T and each C to a G. The next step , consists of “splicing” this DNA sequence into that of another microorganism, for example, a yeast-like fungus, a DNA virus or a bacterium. Now we have to wait. Normally, cells “read” their DNA to follow instructions and to produce from them the molecules that compose them or that they need to function. When the yeast is going to do this, it will find the information to make the virus’s proteins. Like a Trojan horse, we will have used the viral RNA to turn a yeast into a factory. And it may sound like science fiction, but this recombinant technology is the one we use to produce insulin for diabetic patients today or the hepatitis B vaccine, for example. More experimentally, recombinant vaccines have gained some immunity against HIV and even contributed to stopping an ebolavirus outbreak in the Democratic Republic of the Congo.

A promise for the future

Recombinant vaccines are made up of these artificial proteins that, being only fragments of the pathogen, are incapable of producing the disease, but at the same time they are in perfect condition for our immune system to recognize them and develop specific protection against the virus. Another key point is that these vaccines are much faster to produce, and can be ready to test in a matter of weeks instead of months. However, we must bear in mind that, before a vaccine can be applied to the population, it has to go through a multitude of studies that demonstrate its safety and effectiveness. Once the vaccine is synthesized, it must be tested in clinical trials. First in a zero phase with animals to discard the least safe compounds. Once overcome, a phase 1 will be done with human beings, although few, to study its side effects and assess its toxicity. Typically, 90% of drugs fail in this phase, which is where the most advanced SARS-CoV-2 vaccines are now. The next phase brings together more people and assesses the minimum dose from which the effect we seek no longer occurs and establishes a therapeutic range between it and the maximum dose from which toxicity appears. Finally, just before being approved, they will have to pass a third phase with many more subjects to assess the real effectiveness of the vaccine. Even if they are already on the market, they must continue to be controlled in a phase four study to control effects that, due to temporary factors, were impossible to measure in the other phases.

Typically, it can take 10 years for a vaccine to be approved, and as long as it goes ahead, it’s hard to believe that the vaccine can be marketed before the epidemic ends. However, other drugs raised As treatments for infection they are already in phase 2 and 3, because they are compounds previously approved for other diseases whose toxicity and safety are well known. In either case, the drugs may finally arrive on time and help reduce the number of cases. They are a good bet for the future, but we are at a critical moment where the most important factor will not be a molecule or a vaccine, the best way to fight the virus right now is in each one of us, in the decisions we make and in that we help to remain calm. So please stay home and help slow down the curve before the health system collapses. Let’s avoid all possible deaths.

DON’T NECK IT:

  • There is still no vaccine for coronavirus whose effectiveness has been demonstrated in humans. The famous Chinese vaccine has only passed phase zero, which is performed on animals. The passage to phase 1 is overcome by only 90% of the drugs and, even so, a vaccine can take 10 years to go on the market. In an exceptional situation like this, times can be reduced, but it is not prudent to wait for its use to be approved in less than a year. Hopefully the forecasts are wrong, but less than 12 months is quite unfeasible.
  • Vaccines do not produce autism, there is no theoretical reason to think so, and all serious studies done on it have disproved this popular belief. The vaccines on the market maintain high safety standards and their side effects are exceptional and with practically no effects.

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