New research: COVID-19 mutant strain poses a severe challenge to antibodies and vaccines

New research by Tsinghua and other teams: New crown mutants pose a severe challenge to current antibodies and vaccines

New research from Tsinghua and other teams: New crown mutants pose a serious challenge to current antibodies and vaccines New research from Tsinghua and other teams: New crown mutants pose a serious challenge to current antibodies and vaccines

The new crown pandemic has been more than a year, and while vaccination is accelerating globally, mutations of strains in the pandemic have also become the focus of scientists' tracking
.

This poses a certain threat to the current anti-epidemic results and the development of the global epidemic

Recently, "Immunity" (Immunity) published an online study by the Chinese team, entitled "New Coronavirus Mutant Strain Neutralizing Antibody Escape Mechanism and Expanded Use of ACE2 Receptors in Other Species" (Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species)
.

The study confirmed the impact of multiple mutation sites in the spike glycoprotein of the mutant virus strain on the escape of neutralizing antibodies and the use of ACE2 in different species, showing that the mutant strain poses a severe challenge to current antibody therapy and vaccine protection

The findings of this study reveal the impact of the new coronavirus mutant strain on current antibody drugs and serum neutralization capabilities, and provide key information and guidance for the optimization of antibody drugs and the design of next-generation vaccines
.

The corresponding authors of the paper are Professor Zhang Linqi from School of Medicine of Tsinghua University, Professor Wang Xinquan from the School of Life Sciences and Beijing Advanced Innovation Center for Structural Biology, and Professor Zhang Tong from Beijing You'an Hospital of Capital Medical University
.

This is another important work of the team after a series of results of anti-coronavirus research, which provides important scientific basis and guidance for antibody drugs and vaccine optimization

The research team mentioned that since the outbreak of the new coronavirus, research teams around the world have used blood samples from infected persons to isolate high-strength neutralizing antibodies and develop vaccines based on the sequence of the original virus strain.
Now multiple antibody drugs and preventive vaccines have been obtained.
Emergency approval for use (EUA) by the regulatory authorities of the country and the World Health Organization
.

These include Regeneron and Eli Lilly’s antibody cocktail therapy; Pfizer/BioNtech and Moderna’s mRNA vaccines; Johnson & Johnson and AstraZeneca’s adenovirus vector vaccines, as well as China’s inactivated, adenovirus vector and recombinant protein vaccines
.

It is worth noting that as the new coronavirus continues to spread globally, virus mutations continue to accumulate, leading to changes in the antigenicity of epidemic virus strains
.

At the end of last year, the British mutant strain B.

In this study, the research team constructed a total of 28 pseudoviruses including three new coronavirus epidemic mutants, single-point mutations or multiple-point mutations, and evaluated 12 neutralizing antibodies including 7 clinical research antibodies and 23 copies Neutralizing ability of the serum of patients infected with the original strain of new coronavirus (extracted from the plasma of patients with new coronavirus from January to February 2020)
.

Among the 12 kinds of antibodies, 11 are spike protein receptor domain (RBD) antibodies, and one is spike protein N-terminal domain (NTD) antibody.

The study found that among the three mutant strains, the South African mutant strain B.
1.
351 had the most obvious effect on the escape of monoclonal antibodies and convalescent plasma, followed by the Brazilian mutant strain P.
1, and the British mutant strain B.
1.
1.
7 had less impact
.

The study pointed out that this resistance level corresponds to the Y144del and 242-244del mutations in NTD and the K417N/T, E484K, and N501Y mutations in RBD

So far, the most effective monoclonal antibodies isolated from infected and vaccinated individuals often target RBD, and many isolated NTD monoclonal antibodies fail to achieve 100% neutralizing activity
.

These results indicate that RBD antibodies have a greater effect on plasma neutralization

However, the study emphasized that the newly emerging SARS-CoV-2 variants have more and more mutations in NTD and RBD, which will challenge the effectiveness of monoclonal antibody therapy and vaccine protection
.

As far as monoclonal antibodies are concerned, the impact of these mutations is obvious
.

B.

Studies have pointed out that the K417N/T mutation can invalidate most class I antibodies, the E484K mutation can invalidate class II antibodies, and the "K417N-E484K-N501Y" triple mutant can invalidate both class I and class II antibodies
.
These three mutations are all located on the RBD of the new coronavirus S protein.
When these three mutations occur in the virus at the same time, the immune escape ability will be greatly improved
.

It is worth noting that the research team also observed that a single K417N/T mutation tends to increase rather than decrease the neutralizing activity of non-class I monoclonal antibodies
.
Since K417N/T also significantly reduces the binding to ACE2, this mutation may change the balance and facilitate binding to antibodies instead of binding to ACE2
.
The study also found similar results in the recovery period plasma
.

More importantly, the P2C-1F11 antibody currently under clinical research is hardly affected by a single K417N/T mutation or "K417N-E484K-N501Y" triple mutation
.
Previously, Zhang Linqi and others isolated 206 RBD monoclonal antibodies from the cells of patients with new crown infections, and screened out P2C-1F11, P2B-2F6, P2C-1A3 and other high-activity neutralizing antibodies.
The test results were published in "Nature" ( Nature)
.

The study also pointed out that considering that most of the class I antibodies that use heavy chain IGHV3-53/3-66 have no effect on the K417N mutation, the results of P2C-1F11 show that there are class I antibodies that are not affected by the mutation
.
This provides hope for the induction of P2C-1F11-like antibodies through vaccines, which can maintain strong and extensive neutralizing activity against a variety of variants including B.
1.
351 and P.
1
.

It is worth mentioning that at the Pujiang Innovation Forum held recently, Chen Wei , a researcher at the Academy of Military Sciences , vice chairman of the Chinese Association for Science and Technology, and an academician of the Chinese Academy of Engineering, also mentioned the virus mutation issue that is currently of concern to the outside world.
She believes that the current impact on vaccines is relatively large.
It is a South African strain, and a vaccine against this mutation is currently undergoing clinical applications.
I hope that the mutation can be further covered in the future
.

Academician of the Academy of Sciences

In addition, this latest study also found that the new coronavirus through K417N/T, Y453F, E484K, F486L, N501Y and other mutations enhances the ability to use mouse or mink ACE2 to invade host cells
.

They pointed out that this study is not necessarily equivalent to the natural infection and transmission of corresponding animals.
However, the same K417N and/or N501Y mutations found in SARS-CoV-2 adapted mice should cause enough attention.
The mutation may be transmitted to mice and other animals
.

In fact, the SARS-CoV-2 variants previously discovered in Danish mink farms have already raised a warning signal, indicating the host range of the SARS-CoV-2 variants and the complexity of their spread across species
.
Research points out that strict and thorough monitoring of relevant animals is needed to better understand this complexity and prevent future outbreaks
.

The research team pointed out in the discussion section that although the specific level of neutralizing antibodies required to provide protection is still uncertain, the decrease in antibody titer has raised concerns about its potential for protection against emerging variants, especially B.
1.
351
.
In fact, studies have pointed out that the decrease in patient antibody titers is related to the increase in the possibility of re-infection
.

The research team concluded that these results indicate that antigen transfer is occurring in the newly emerging SARS-CoV-2 variant
.
This requires immediate reassessment and update of monoclonal antibody therapies and vaccines
.
In the long term, the goal is to develop universal treatment and preventive interventions to maintain effectiveness against all mutant strains
.

"Before this day arrives, controlling the emergence of new variants requires speeding up the introduction of vaccines and active practice of public health measures that have been proven effective
.
" The study wrote
.

Link to the paper: https:// href="/news/sub2.
aspx?id=3570" target="_blank" style="color:#ba1413">Focus on the new crown pneumonia epidemic