COVID-19 mutations vs. vaccines: a battle of breakthrough and encirclement

At present, while the new crown vaccines have been approved for marketing or emergency use and large-scale vaccination is being carried out, the new coronavirus is also fighting tenaciously in the form of mutations. A tug-of-war between prevention and escape has begun and is becoming increasingly fierce.

What impact will the mutation of the new coronavirus have on the epidemic and the effectiveness of vaccines? How should we view the mutation of the new coronavirus?

Why is the new coronavirus prone to mutating?

Since the outbreak of the COVID-19 pandemic, there have been thousands of reported mutations of the coronavirus, with more than 4,000 mutations in the spike protein alone. So why is the coronavirus so prone to mutation?

In fact, heredity and variation are the basic characteristics of life. Variation exists in all organisms in nature. It is an important way for organisms to adapt to the environment and maintain survival, and it is a universal law of biological evolution. However, the variation rate of different species is different.

Viruses are extremely simple organisms. Because they have no cell structure, their genetic material is easily affected by the external environment and the molecular environment within the cell and changes. Therefore, compared with other organisms, the genetics of viruses have greater variability. Among viral mutations, the spontaneous mutation rate of RNA virus genomes is higher due to low replication fidelity and lack of proofreading activity of replication enzymes. Today, the new coronavirus that is raging around the world is an RNA virus, which is why it mutates so frequently.

What are the mutations of the new coronavirus?

There are currently four new coronavirus variants that have a large impact and have become a certain epidemic: the D614G variant of the new coronavirus that appeared in Europe, the B.1.1.7 variant of the new coronavirus found in southern England and the London area, the B.1.351 variant found in South Africa, and the P.1 variant of the new coronavirus found in Brazil.

The World Health Organization's weekly epidemiological report released on January 27 pointed out that the British variant of the new coronavirus has appeared in 73 countries and regions. The two local confirmed cases reported in Daxing, Beijing not long ago also belonged to the British B.1.1.7 strain after whole genome sequencing and analysis.

It can be seen that among the current variants of the new coronavirus, the B.1.1.7 variant has the largest impact. Compared with the original new coronavirus, the binding affinity of its S protein to the human ACE2 receptor has increased by 1,000 times, and the transmission speed is as high as 70% higher than the previous strain. The main reason for its fast transmission speed and increased affinity is that a mutation N501Y occurs in the six key interface amino acids of the receptor binding structure (RBD) of the new strain, and a P681H mutation occurs adjacent to the Furin protease cleavage site, resulting in reduced stability of the S protein after cleavage, exposing the open domain, making it easier for the S protein to bind to the human ACE2 receptor.

The virus has mutated. Is the vaccine still effective?

Global and widespread vaccination is becoming one of the important means to control the development of the COVID-19 pandemic. So, will the mutated COVID-19 virus affect the effectiveness of global vaccination?

According to the latest information released by the World Health Organization, based on the global monitoring of the new coronavirus mutations, there is no evidence that the virus mutations will make the existing new coronavirus vaccines ineffective.

Generally speaking, vaccines target early versions of the virus, and even if the virus mutates, its genetic sequence is still very similar to the early version. In addition, as an RNA virus, the new coronavirus mutates frequently by nature, but most mutations are meaningless and do not cause major changes in the encoded protein.

According to current research results, the mutation of the new coronavirus is still within a normal range, and no impact on the effectiveness of the vaccine has been found.

In addition, the World Health Organization has set up a special SARS-CoV-2 virus mutation and evolution working group in the global coronavirus laboratory network, which is timely and rapidly detecting new mutations of the virus and assessing their possible impact. This will also provide early warning and scientific analysis basis for the subsequent development and application of vaccines.

How cunning is the new coronavirus?

Although there is currently no evidence that virus mutations will make existing new coronavirus vaccines ineffective, studies have found that in addition to the currently clear obvious increase in the transmission ability of the new strain, what remains to be confirmed is the ability to evade human immunity and antigenic drift.

Not long ago, the Gupta Laboratory of Cambridge University showed the original data of the changes in the protection of Pfizer's new crown vaccine against the mutant strain B.1.1.7. The results showed that 21 days after vaccination, the neutralizing ability of the vaccine recipient's serum decreased significantly. Researchers from the National Institute for Communicable Diseases (NICD) of South Africa also published a paper stating that the new crown variant B.1.351 that appeared in South Africa can significantly escape the attack of three related monoclonal antibodies. In a study of 44 sera from recovered patients with new coronary pneumonia, it was found that 21 sera (48%) completely lost their ability to bind to the B.1.351 mutant strain. This shows that the new coronavirus is far more cunning than we imagined, and it deserves our high attention.

In addition, the three mutants discovered so far all have N501Y mutations, which increases the binding of the new coronavirus to ACE2, thereby accelerating the spread of the virus. Although the transmission characteristics and lethality of the mutants B.1.351 and P.1 are still unclear, genetic analysis shows that they both have E484K and K417N mutations, which may cooperate with the N501Y mutation to make the virus more easily bind to human cells. These research findings all suggest that the viral epitopes may have undergone immune escape or antigenic drift.

Regarding the new coronavirus mutation, Fauci, director of the National Institute of Allergy and Infectious Diseases, also emphasized at an online dialogue that the evolution of the new coronavirus variant should be taken very seriously. He also called on countries to accelerate vaccine upgrades. In short, there is still a long way to go to completely defeat the cunning new coronavirus.

In view of the current development of the epidemic, the trend of new coronavirus mutation and the large-scale use of new coronavirus vaccines, we should maintain a clear understanding and correctly view vaccination. After vaccination, even if the virus escapes due to antigen evolution, some of the pre-existing residual immune response will reduce symptoms.

Similarly, we should not take it lightly after vaccination and continue to strengthen prevention and control, wear masks, and wash hands frequently. I believe that through good personal protection and the efforts of scientific researchers, we will be able to control the development of the epidemic and ultimately defeat COVID-19!

Author: Contributed by Yaohuluwa Medical Biotechnology Popular Science Group