Omi Keron swept the world, and 5 "Nature" articles revealed on the same day: How useful are vaccines and antibodies?

▎Editor of WuXi AppTec's content team Since it was discovered in samples from South Africa and other places in early November, a new mutant strain of the new coronavirus, Omicron, has quickly become the focus of the world
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In just over a month, Omi Keron has spread rapidly around the world, and is expected to soon replace the current delta mutant strain and become the world's most important new coronavirus lineage
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Compared with the previous mutant strains, Omi Keron has a larger number of key mutations, which has also caused widespread concern
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Omikeron’s spike protein contains as many as 32 mutations, 15 of which are located in the receptor binding domain (RBD), and there are many mutations that can enhance the ability of the virus to bind to cells
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The WuXi AppTec content team should know that the RBD of the spike protein is the key area that binds to human cells when the new coronavirus invades the human body
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At the same time, they are also important targets for scientists to develop vaccines and neutralizing antibody therapies
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Therefore, people can't help but worry: Is Omi Keron's ability to escape vaccines and neutralizing antibodies stronger? Are existing vaccines and therapies effective against Omi Keron? A few days ago, the "Nature" website published 5 papers online at the same time, and these papers have been accepted by the "Nature" magazine
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In these studies, Chinese and foreign scientists have paid attention to the effectiveness of existing vaccines and antibodies against Ome Keron from different angles.
While revealing the strengthening of Ome Keron’s ability to escape, it also pointed out the direction of human war against the new crown virus
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In one of the studies, the team of Professor Dayi He from Columbia University found that the effect of existing vaccines and monoclonal antibody therapies on Omi Keron has been greatly reduced, but the vaccine booster and some monoclonal antibodies can still play an important role
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The research team tested the effects of four vaccines that are currently widely used in the world-Pfizer/BioNTech vaccine, Modena vaccine, Johnson & Johnson vaccine and AstraZeneca vaccine-on the prevention of Omikeron
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They collected blood samples from 39 participants who had received two full doses of the vaccine and tested their neutralizing activity against Omi Keron
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The results showed that the neutralizing antibody titers of all 39 participants decreased significantly.
For example, the neutralizing activity of Pfizer/BioNTech vaccine and Modena vaccine vaccinators decreased to 1/21 and 1/8.
6 of the original strain, respectively
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This shows that the effectiveness of these four vaccines in preventing Omi Keron has been significantly reduced, including two participants who have been infected with the new coronavirus
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However, this experiment also showed positive results
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In addition to the 39 participants who received two doses of the vaccine, the experiment also included 15 participants who received Pfizer/BioNTech or Modena booster shots
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The results showed that the neutralizing antibodies of these people also decreased, but the decrease was smaller than that of the participants who received the two doses of the vaccine
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▲The impact of different vaccines on the effectiveness of preventing Omi Keron (picture source: reference [3]) In addition, the research team also tested 19 monoclonal antibodies, including 9 therapeutic antibodies that have been clinically approved , Other monoclonal antibodies that have received attention, and the monoclonal antibodies being developed by Professor Dayi He’s team
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The results showed that 17 of the 19 monoclonal antibodies completely or partially lost their neutralizing ability, but the two approved monoclonal antibodies (romlusevimab and sotrovimab) still retained their neutralizing activity
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The paper pointed out that Omi Keron poses a severe threat to the existing new crown vaccines and therapies, and the effect of interventions that only target spike proteins is declining
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Therefore, the scientific community needs to change its strategy, predict the evolution direction of the virus, and develop new interventions for more conservative areas of the virus
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In another paper, the team of Professor Xie Xiaoliang of Peking University, in collaboration with scientists from the Institute of Biophysics, Chinese Academy of Sciences, China Institutes for Food and Drug Control and other institutions, used a new screening technique to map the mutations of the Omikeron spike protein RBD.
Atlas
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Omi Keron has 15 mutations in the spike protein RBD, and mutations in these key positions are likely to enhance the virus's ability to escape antibodies
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In this study, Professor Xie Xiaoliang's team screened 247 human neutralizing antibodies and used a new high-throughput yeast display technology to detect the ability of mutation escape antibodies
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Studies have found that these human neutralizing antibodies can be classified into six AF categories based on epitopes (antibody binding sites), and a single mutation on the Omi Keron RBD will weaken the effects of different types of neutralizing antibodies
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Especially for AD antibodies, the epitopes of these antibodies overlap with ACE2 binding motifs, so Omi Keron can escape through four important mutations
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The E and F antibodies have broad-spectrum neutralizing activity against the Sarbecovirus subgenus (sarbecovirus), so they are less affected, but there are still 3 mutations that can help the virus escape some of the antibodies
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Overall, in this study, Omi Keron can evade 85% of human neutralizing antibodies
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In the testing of monoclonal antibody therapies, the author also found that Omi Keron can greatly weaken the effects of various therapies, while the monoclonal antibodies sotrovimab and DXP-604 can still work, but the effect has declined
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In the third paper, the Africa Health Research Institute (Africa Health Research Institute) isolated and sequenced the Ome Keron live virus from an infected person in South Africa, and then tested whether the blood samples of 19 vaccinated people could still Effectively neutralize new variants
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These participants were all vaccinated with Pfizer/BioNTech's BNT162b2 vaccine, and some of them had been infected with the “old version” of the new coronavirus before vaccination, and their serum had significantly stronger neutralizing activity against the original new coronavirus
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However, regardless of whether there is a history of infection, Omi Keron variants can have a significant escape effect on vaccine-induced antibodies
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Compared with the neutralizing activity of the antibody against the original new coronavirus strain, the neutralizing activity of Omi Keron is 22 times different
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In this paper, the researchers also verified that the Omi Keron variant, despite multiple mutations, still needs to bind to the ACE2 receptor to infect cells
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The research team led by the Institut Pasteur in France isolated the Omi Keron virus strain from a patient in Belgium, tested 9 therapeutic neutralizing antibodies and 115 sera from vaccinated or recovered patients
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The results also showed that the new variant has a large number of escapes in the neutralization of antibodies
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Among the 9 monoclonal antibodies that have been approved for clinical use or are under development, 5 are ineffective against Omi Keron, 2 have only 1/20 of neutralizing activity against the Delta variant, and 1 has a reduced neutralizing activity 2/ 3.
It shows that the new variant can completely or partially resist the neutralizing effect of these therapeutic monoclonal antibodies
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Five months after receiving two doses of vaccines (from Pfizer/BioNTech or AstraZeneca), the serum failed to detect antiviral activity against Omi Keron
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Similarly, 6 months or 12 months after the onset of symptoms, the survivors have very low or no neutralizing activity for Omi Keron
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However, the antibodies in the serum of individuals who received the third booster shot and two more shots of the vaccine after infection can still neutralize Omi Keron, indicating that the vaccine booster may enhance the ability to neutralize Omi Keron
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In the last paper, a research paper by Vir Biotechnology, which focuses on the development of infectious disease treatments, and the University of Washington in the United States showed evidence that Ome Keron’s immune escape ability may be stronger than the previous new coronavirus lineage, and “broad spectrum "Neutralizing antibodies can respond to the transformation of Omi Keron antigen and achieve high-efficiency neutralization
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Compared with the original new coronavirus strain, Omi Keron’s RBD has 15 amino acid substitutions, and the binding affinity of RBD to human ACE2 is increased by about 2.
4 times
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 The research team tested the neutralizing activity of more than 40 monoclonal antibodies that have been approved or are in development through the Ome Keron pseudovirus (a new coronavirus model)
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Among the 29 mAbs targeting specific regions of RBD (receptor binding motifs), most of them had a significant decrease in neutralizing activity against Omi Keron, and only 3 types still had neutralizing activity, including S2K146 mAb1 that mimics ACE2
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In addition, there are some broad-spectrum neutralizing antibodies that can neutralize a wide range of virus species in the Sarbe coronavirus subgenus.
This study shows that some of these antibodies can recognize antigens other than the receptor binding motif.
Epitopes to neutralize Omi Keron, including S2X259, S2H97, and sotrovimab also revealed in the research of Professors Dayi He and Professor Xie Xiaoliang
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The paper pointed out that such broad-spectrum neutralizing antibodies may prove to be the key to controlling the ongoing pandemic and future zoonotic spillovers
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 Photo source: 123RF When we were looking forward to the immune defense line built by vaccines to prevent the spread of the virus, the emergence of Omi Keron gave people a blow, and even made people worry about whether the defense line we built in two years will collapse? But as these 5 papers have shown, in the face of another round of impact from the virus, the determination and speed of the global scientific community can still give us confidence.

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From the World Health Organization's announcement of Omi Keron as a "new crown variant worth paying attention to" at the end of November, to the acceptance and publication of these five papers, in less than a month, scientists unveiled Omi Keron's mystery
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We have seen that some existing vaccines and therapies have been weakened, but we have also screened out intervention strategies that are still effective
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Equally important, these studies also guide the direction of research for other mutants that may appear in the future
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We believe that science will allow us to pass the cold wave of Omi Keron smoothly, and the winter of the new crown virus will eventually come to an end
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Reference: [1] Lihong Liu et al.
, (2021) Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.
Nature Doi: https://doi.
org/10.
1038/d41586-021-03826-3 [2] Yunlong Cao et al.
, (2021) Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.
Nature Doi: https://doi.
org/10.
1038/d41586-021-03796-6[3] Sandile Cele et al.
, (2021) Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization.
Nature Doi: https://doi.
org/10.
1038/d41586-021-03824-5[4] Delphine Planas et al.
, (2021) Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.
Nature Doi: https://doi.
org/10.
1038/d41586-021-03827-2[5] Elisabetta Cameroni et al.
, (2021) Broadly neutralizing antibodies overcome SARS- CoV-2 Omicron antigenic shift.
Nature.
Doi: https://doi.
org/10.
1038/d41586-021-03825-4