According to the World Health Organization (WHO), more than 27 million people worldwide have been infected with the new coronavirus. At the same time, drug and vaccine research and development for COVID-19 in the biopharmaceutical industry is progressing rapidly. At present, there are several new crown candidate vaccines and antibody therapy into phase 3 clinical trials. However, we know that the virus genome is constantly mutated, the new coronavirus is no exception, there are now more than 95,000 new coronavirus genome sequences in GISAID’s new coronavirus database.
One concern is whether the mutation of the new coronavirus will invalidate the new crown vaccine, which is currently under development. Today, the Pharmaceutical Mingkang content team will discuss this issue in conjunction with public information.
How fast is the genome mutation of the new coronavirus?
The new coronavirus is a single-stranded RNA virus containing nearly 30,000 bases, and RNA viruses are more likely to introduce mutations during replication than DNA viruses. However, the new coronavirus does not mutate very quickly compared to the coronavirus that causes certain common colds, as well as the HIV virus that causes AIDS. This may be due to the more complex mechanism of genetic mutation correction in the new coronavirus. Although genetic mutations can help the virus produce mutations, if there are too many mutations in the genome, it can lead to protein formation and virus replication. The gene mutation correction mechanism of the new coronavirus can modify the errors introduced in RNA replication to keep the virus replication going normally.
As we may know, many of the current antiviral therapies, many of which are nucleoside analogas, are ineffective against the new coronavirus, and they interfere with RNA replication by embedding nucleosides in the RNA sequence that make up the RNA in place of the RNA. The new coronavirus’s error-correcting mechanism has made most nucleoside antiviral therapies “reactive”, but this mechanism that makes it resistant to antiviral therapy also makes the genome of the new coronavirus more stable. Dr Emma Hodcroft, a molecular infectious diseases scientist at the University of Basel, says the genome of the new coronavirus accumulates about two single-base mutations each month, one-half the rate of the coronavirus that causes the common cold and a quarter of the HIV virus.
Will a genetic mutation in the new coronavirus invalidate the new crown vaccine?
The new corona vaccine’s action is to make the body’s immune system produce a median antibody and cellular immune response to the new coronavirus antigen. If the genome of the new coronavirus mutates, some genetic mutations could theoretically alter the composition of the antigen protein, preventing antibodies produced by the immune system from identifying and binding antigen proteins (such as the hedgehog protein on the surface of the new coronavirus), thereby neutraling the antibody. So, in the real world, has this type of mutation occurred with the new coronavirus?
In a scientific paper published recently in PNAS, researchers analyzed the genomes of 18,484 new coronavirus viruses and found that the sequence of pyrethroid proteins encoding the new coronavirus was very stable, with the most significant mutation being the D614G mutation, which occupies the no. 614 position in the earliest new coronavirus protrusion protein. After the mutation, the position becomes glycine (G). The new coronavirus, which carries this mutation, is now dominant globally. However, this mutation is located in the binding part of the hedgehog protein S1 sub-base and S2 sub-base and is not easily identified by antibodies. As a result, the researchers speculate that the mutation does not affect the binding of antibodies to prickly proteins.
In addition to the D614G mutation, the second highest number of genetic variants on the hedgehog protein was a synonym variant (the gene sequence changed, but the amino acids produced did not change), with a frequency of only 1.96%. A comparison of the different prickline protein sequences showed that the difference between the new coronavirus sequences found in infected patients and the baseline sequence was only 0.55 base mutations. The data mean that there are not many genetic mutations in the viruses that currently exist around the world that can disable vaccines.
This conclusion has also been validated in the development of meso-antibodies, both in the development of Vir Biotechnology and Regenerative Antibodies, which have a meso-effect on almost 100% of new coronavirus strains in preclinical trials.
Moreover, the new coronavirus usually stimulates a variety of different antibodies in the body against the new coronavirus antigen, which are combined with different tables of the antigen protein, making it more difficult for the new coronavirus to evade the role of the antibody through genetic mutations.
Will a new coronavirus gene mutation that invalidates the vaccine be produced in the future?
Current scientific studies have shown that the genetic variants already produced in the new coronavirus do not significantly affect the effectiveness of the antibodies and the new coronavirus vaccine. However, historical experience has shown that drug resistance can be produced, and antibiotic resistance to bacteria is currently a major challenge in the field of global health. So is it possible for the new coronavirus to gradually gain the ability to evade the vaccine-inspired immune response, just like drug-resistant bacteria?
The answer to this question starts with the mechanism of natural selection. Natural selection refers to the fact that a species carrying certain genetic mutations has a survival advantage due to a certain selection pressure, resulting in an increasing proportion of the entire population. In the case of antibiotic resistance in bacteria, for example, bacteria that carry mutants of resistance usually only appear after people abuse antibiotics, because the pressure of choice from antibiotics makes them “stand out” in this environment. In an antibiotic-free environment, these bacteria, which carry mutants of resistance, do not show a survival advantage over other bacteria.
Map of the natural selection process of drug-resistant bacteria (Photo: Wykis / Public domain)
Although scientists have now discovered new coronavirus strains that can evade certain antibody effects, they are still very rare in the global population. Since most people in the global population are not immune to the new coronavirus, their immune systems are not yet able to exert selective pressure on the reproduction of the new coronavirus. This means that these genetic mutations, which are potentially resistant to vaccines, are not yet available.
To be sure, if the new crown vaccine succeeds in increasing the immunity of people around the world to the new coronavirus, the number of new coronavirus strains carrying mutations in the immune escape gene may gradually increase under the pressure of immune selection. As a result, scientists still need to closely monitor the emergence of new genetic mutations.