Santiago Ramón y Cajal used to say almost a century ago that “the millennial struggle between the microbe and man is reduced to a simple question: who tames whom” . Well, today that confrontation has intensified, and SARS-CoV-2 , the virus that causes the disease known as COVID-19, has managed to quarantine a large part of the world’s population. In recent weeks, one of the many doubts that this disease has raised is whether the pathogen that causes it can mutate and, if it did, whether such a thing would make it more dangerous. But to answer this question, we must first understand what we are dealing with.
The SARS-CoV-2 genome, which belongs to the betacoronavirus family, is made up of a single ribonucleic acid (RNA) chain made up of some 30,000 nucleotides – the organic molecules that make up its building blocks. There are also DNA viruses, but RNA viruses are mutated more often. This occurs because, unlike the former, they lack mechanisms to correct errors that may arise during the replication process.
However, according to Raúl Ortiz de Lejarazu, professor of Microbiology and emeritus director of the National Influenza Center, the SARS-CoV-2 genome is so large – it is one of the largest of its kind – that some parts of it remain longer. stable, so their mutation capacity would be less than that of most RNA viruses . It would also contribute to this that it does seem to have a fault correction system , as some studies point out.
“In any case, the presence of one or more mutations does not necessarily imply that it will be more lethal, ” says Ortiz de Lejarazu. In fact, until now, none of the ones that SARS-CoV-2 has presented can be related to it; they do not even appear to favor its infectious capacity or increase antigenic difference, that is, the ability of the virus to prevent the host’s immune system from easily identifying and rapidly destroying it. Moreover, it is even possible that mutations occur that cause the virus to evolve into less aggressive forms.
In any case, knowing them can provide us with very important data to try to determine its origin or how it has spread, what experts call the traceability of the virus. “This is done by analyzing its genome and comparing it with other sequences that are already published,” says Ortiz de Lejarazu.
The WHO has registered 35 possible vaccines to try to combat SARS-CoV-2 , but, at the moment, they are still under study , so we will have to wait to know if they can be administered. So when could we have one? Experts clarify that it will not be immediately . After conducting basic research in the laboratory and finding out which antigens might be helpful in preventing disease – the substances that induce an immune response in the body and cause antibodies to be generated – we need to experiment in tissue culture and in animals ; It is the so-called preclinical phase. If this is successful, it leads to the clinic, where the candidate vaccine is tested in humans. Ortiz de Lejarazu explains: “The first tests are for safety, to see if the desired protection is really achieved and if the doses are adequate.” However, from the time that candidate vaccine is administered until immunity is generated, three to four weeks may elapse.
Then come the trials in phases II, III and IV, in which the optimization of the processes is sought and tests are carried out with larger groups of the population and in people of more advanced ages. Finally, approvals would still need to be obtained from each country’s drug agencies. Only in this way would it be possible to start large-scale production of the treatment and its distribution
Vaccine prototypes
Since the COVID-19 outbreak in Wuhan became known, the National Center for Biotechnology of the Higher Council for Scientific Research (CNB-CSIC), under the coordination of virologist Luis Enjuanes, began the procedures to produce a vaccine. “The Enjuanes team tries to develop an attenuated coronavirus through genetic engineering ,” highlights Mariano Esteban Rodríguez, head of the Poxvirus and Vaccines Group at the CNB-CSIC and advisor to the Gadea Foundation for Science. The members of the laboratory in charge of this expert are also working on a vaccine, in his case based on viral vectors. In essence, it is about using a modified virus that acts as a vehicle to introduce genetic material into the nucleus of a cell. In this way, when it enters the body, it elicits an immune response and antibodies are generated .
Live vaccines are usually the most effective , as they allow the development of immunity against all viral components. In them, the virus is so weakened that our natural defenses, if healthy, can easily defeat it. But they are not the only ones that exist. Nucleic acid vaccines , made from DNA and RNA, make the antigen in the body itself. “ RNA ones, in particular, are very safe ; They have no adverse effects and are proving to be effective in certain cancers and against certain pathogens. In fact, they are already being tested in clinical phases against the coronavirus, ”says Esteban Rodríguez. It is also possible to use purified antigens. These, as indicated by this CNB-CSIC specialist, are mixed with an adjuvant to enhance or direct the immune response against a certain antigen. Some vaccines that use this strategy are also in clinical stages.
By Marta Riesgo.
