COVID-19 vaccine by Fosun Pharma/BioNTech still effective against N501 mutant strains

COVID-19 vaccine by Fosun Pharma/BioNTech still effective against N501 mutant strains. On December 19, 2020, British Prime Minister Boris announced the cancellation of the Christmas reunion plan, and London and other areas entered the most stringent level 4 blockade. In order to prevent the further spread of the epidemic, many countries announced the prohibition of navigation with the United Kingdom. The scientific adviser of the British government stated that the new mutant strain is raging in London and its infectious power is 70% higher than before.

Why does the UK mutant strain cause concern?

The British mutant strain was named VUI-202012/01. It was first discovered in London and Kent in mid-September 2020. According to its mutation characteristics, the strain was divided into a new lineage B.1.1 in the phylogenetic tree. 7.

In December, B.1.1.7 lineage virus infections were continuously detected in the United Kingdom. At present, most strains generally have a few mutations compared to the original strain, but there are many mutation sites accumulated in the B.1.1.7 lineage, mainly 6 synonymous mutations, 14 non-synonymous mutations and 3 deletion mutations, the evolution speed is abnormal.

Among the 23 mutations in the B.1.1.7 lineage, the most noteworthy mutation site is the key amino acid mutation N501Y in RBD (receptor binding region). This site is particularly important and is one of the 6 key contact residues of RBD. One. The N501Y mutation increases the binding affinity of SARS-CoV-2 to ACE2, which may enhance the ability of the virus to enter the human body.

As early as September, scientists posted on the cell that the N501 mutation will reduce the polarity of key residues in RBD and increase the affinity of the virus with the ACE2 receptor on the surface of human cells. This mutation also enables a strain that does not infect mice to infect mice. The continuous passage of the virus in the lungs of mice will cause adaptive mutations of the virus, which enhances the infectivity of the virus.

Will a mutated virus become a vaccine nemesis?

Vaccines are considered to be a global means to effectively control or even end the epidemic. This mutation has caused people to worry about whether the existing vaccines still have a protective effect.

On January 7, 2021, researchers from Pfizer and the University of Texas Medical Branch published the latest research on bioRxiv, showing that it was jointly developed by Shanghai Fosun Pharmaceutical and BioNTech of Germany. The mRNA COVID-19 nucleic acid vaccine BNT162b2 still has a neutralizing effect on the virus strains carrying N501Y gene mutations.

The researchers mutated the N501 strain USA-WA1/2020 used in the research and development of BNT162b2, resulting in the syngeneic Y501 SARS-CoV-2; the 20 serum samples used in this study came from the vaccine subjects of the BNT162b2 clinical trial The 20 subjects received two doses of vaccine 21 days apart, and blood samples were collected 2-4 weeks after vaccination.

The researchers used 20 serum samples to test the neutralization titers of the standard strain N501 and the variant strain Y501. The results showed that the ratio of the serum neutralizing antibody titer against the Y501 virus to the neutralizing antibody titer against the N501 virus was 1.46 , Indicating that the neutralizing ability of the serum against the mutant strain did not decrease, or even higher, indicating that BNT162b2 is still effective against the mutant strain N501Y.

 
Figure: Comparison of 50% neutralization titers of 20 serum samples for N501 (black) and Y501 mutant (red)

Zhang Wenhong, director of the Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan University, said, “Without natural selection, there will be no virus evolution. Similarly, without the pressure of vaccines, it is basically impossible to naturally screen out virus variants that are ineffective against vaccines. At present, vaccines produce a lot of S protein For antibodies in the region, a single mutation (such as the previous D614G mutation and the recent N501Y mutation) is unlikely to reduce the effectiveness of the vaccine.

Mutations in the viral genome are common, and some mutations in the viral genome can change the virus’s ability to spread and its resistance to neutralizing antibodies. However, it usually takes years, not months, for viruses to evolve to the point where existing vaccines are ineffective.

mRNA vaccine technology can quickly respond to virus mutations, and a new mRNA vaccine can be designed in as short as 6 weeks

In addition to the N501Y mutation, other mutations in the VUI-202012/01 strain are yet to be studied. The British mutant not only increases the infectivity of the new coronavirus, we need to pay more attention to its potential impact, that is, the new coronavirus may exhibit “antigen drift” like influenza viruses. If there are antigens that cannot be neutralized by existing vaccines Drift, you need to adjust the existing vaccine.

Compared with traditional vaccines, mRNA vaccines have absolute advantages in the development cycle. The advantage of this technology platform is that only the nucleic acid sequence encoding the S protein needs to be changed to quickly produce vaccines against new virus strains. The technical barrier of mRNA vaccines lies in delivery, and companies such as BioNTech and Moderna have a deep professional knowledge base and excellent professional technology, so that the mRNA vaccine can be completed within 1-2 months from design to sample preparation, which makes the COVID-19 vaccine Iterative updates are easier.

“Once a major mutation in the virus is monitored, a new mRNA COVID-19 vaccine will be provided within 6 weeks.” said Dr. Ug Sain, co-founder of BioNTech in Germany.

The domestic COVID-19 inactivated vaccine is also undergoing research on this mutant strain, and the results are expected to be announced soon.

(source:internet, reference only)

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