Santiago Ramón y Cajal said 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 much of the world’s population. In recent weeks, one of the many doubts that this disease has raised is whether the pathogen causing it can mutate and, if so, whether such a thing would make it more dangerous. However, to answer this question, we must first understand what we are facing.
The SARS-Cov-2 genome, which belongs to the beta-coronavirus family, is made up of a single ribonucleic acid (RNA) chain composed of about 30,000 nucleotides - the organic molecules that make up its core parts. There are also DNA viruses, but RNA viruses experience mutations more frequently. This is because, unlike the former, they lack mechanisms to correct errors that may arise during the replication process.
However, as explained by Raúl Ortiz de Lejarazu, professor of microbiology and director emeritus of the National Flu Center, the genome of SARS-Cov-2 is so large-it is one of the largest of its kind-that parts of it remain more stable, so their mutation capacity would be lower than that of most RNA viruses. It would also contribute to the fact that it does appear to have a system for correcting errors, as some studies point out.
"However, the presence of one or more mutations does not necessarily imply that it will be more lethal," said Ortiz de Lejarazu. In fact, so far, none of the ones that have submitted SARS-Cov-2 can be related to it; they do not even seem to favour their infectious capacity or increase the antigenic difference, that is, the ability of the virus to prevent the host’s immune system from easily identifying it and rapidly destroying it. Moreover, mutations may even occur that cause the virus to evolve into less aggressive forms.
In any case, knowing them can give us very important data to try to determine their origin or how they have spread, what experts call the traceability of the virus. "This is done by analysing its genome and comparing it with other sequences that are already published," states Ortiz de Lejarazu.
WHO has registered 35 potential vaccines to try to combat SARS-Cov-2, but they are still being studied for the time being, so it will be necessary to wait to see if they can be administered. So when could we have one? Experts make it clear that it will not be immediately. After conducting basic laboratory research and finding out which antigens might be useful in preventing the disease-substances that induce an immune response in the body and cause antibodies to be generated-, it is necessary to experiment in tissue cultures and in animals; it is the so-called preclinical phase. If this is successful, it is given to the clinic, where the vaccine is tested on humans. Ortiz de Lejarazu explains: "The first tests are for safety measures, to see if you really get the desired protection and if the doses are adequate.” However, it can take three to four weeks from the time that the vaccine is given until immunity is generated.
This is followed by phase II, III and IV trials, which seek to optimise processes and carry out tests on larger population groups and older people. Finally, approvals should still be obtained from the drug agencies in each country. Only then would it be possible to start large-scale production of the treatment and its distribution.
Prototypes of the vaccines
Since the outbreak of COVID-19 in Wuhan became known, the National Center for Biotechnology of the Higher Council for Scientific Research under the coordination of virologist Luis Enjuanes, began the process to produce a vaccine. "The Enjuanes team is trying to develop an attenuated coronavirus by genetic engineering," says Mariano Esteban Rodríguez, head of the Poxvirus and Vaccines Group at the centre and advisor to the Gadea Foundation for Science. The laboratory members in charge of this expert are also working on a vaccine, possibly based on viral vectors. In essence, it’s about using a modified virus that acts as a vehicle to introduce genetic material into a cell nucleus. Thus, when it enters the body, it elicits an immune response and antibodies are generated.
Some researchers try to use a weak version of the virus to activate an immune response in the body.
Attenuated 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 defences, if healthy, can easily defeat it. However, they are not the only ones that exist. Nucleic acid vaccines, created from DNA and RNA, produce the antigen in the body itself. "RNA, in particular, is very safe; it has no adverse effects and is proving effective in certain cases of cancer and against certain pathogens. In fact, they are already being tested in clinical phases against the coronavirus,” explains Esteban Rodríguez. It is also possible to use purified antigens. These, according to this CNB-CSIC specialist, are mixed with an adjuvant to potentiate or direct the immune response against a given antigen. Some vaccines using this strategy are also in clinical stages.