Cell is heavy!

The mutant strain of Life science Omi Keron spreads wantonly and is sweeping through most countries and regions around the world at a tsunami-like speed, bringing new challenges to the health systems of all countries
.

Recently, Cell has successively published two latest studies on antibodies against Omi Keron mutants.
Both papers both pointed out the positive effects of the third dose of vaccine on Omi Keron mutants
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The team of Stefan Pöhlmann from Georg-August-University Göttingen and German Primate Center published an article titled "The Omicron variant is highly resistant against antibody-mediated neutralization – implications for control of the COVID-19 pandemic"
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The study reported that the new coronavirus Omi Keron variant is resistant to several therapeutic antibodies and can effectively escape antibodies induced by previous infections or two injections of Pfizer vaccine (BNT162b2)
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In contrast, the antibodies induced by the three-shot Pfizer vaccine or the mixed inoculation of the Oxford-AstraZeneca/Pfizer vaccine (ChAdOx1/BNT162b2) can more effectively neutralize the Omi Keron mutant strain
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The team of Alejandro B.
Balazs from Ragon Institute of MGH, MIT, and Harvard published an article titled "mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS in Cell Press.
-CoV-2 Omicron variant" new research
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Research reports that the Omi Keron variant can escape the humoral immunity induced by the vaccine, but the humoral immunity induced by the third shot of the mRNA vaccine can cross-neutralize the virus
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In addition, compared with other strains, pseudoviruses with Omi Keron spikes show a more effective transduction effect on target cells expressing ACE2
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Long press the picture to identify the QR code to read the original text.
Omi Keron mutant strain is highly resistant to antibody-mediated neutralization-its impact on the control of the new crown pandemic.
Research highlights Omi Keron uses human and animal ACE2 to enter Host cells; Omi Kiron is resistant to the neutralization of several therapeutic antibodies; Omi Kiron can effectively escape antibodies from infected persons or two doses of Pfizer vaccine; Omi Kiron can escape moderately Vaccination with three doses of antibodies induced by Pfizer or a heterologous vaccine
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Research Introduction Vaccination is considered to be the key to ending the devastating new crown pandemic
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However, the unfair distribution of vaccines and the emergence of mutant strains of the new crown threaten the effectiveness of this method
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In the past year, several "SARS-CoV-2 variants of concern" (SARS-CoV-2 variants of concern) have emerged around the world.
At present, the main strain of the global new crown pneumonia epidemic is the delta variant
.

These variants of concern show stronger infectivity and/or immune escape ability, and these characteristics are related to the mutation of the viral spike protein
.

 The spike protein of coronavirus helps the virus to enter the host cell and is the core target of virus neutralizing antibodies
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Mutations in the N-terminal domain (N-terminal domain) containing the antigenic supersite and the receptor binding domain (receptor binding domain) that bind to the ACE2 receptor can be achieved by changing the neutralizing antibody epitope Resistance to neutralization
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But which mutations in the spike protein will increase the spread of the virus, and what is the specific mechanism? We are not very clear about this issue, although researchers have determined that the D614G mutation promotes the spread of the virus and the participation of ACE2
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Recently, a new “mutant strain requiring attention” was discovered in South Africa, namely Omi Keron (B.
1.
1.
529, BA.
1 and BA.
2).
Its emergence is related to the rapid increase of new infections and hospitalizations.
There is a correlation between the increase
.

Omi Keron was introduced to several European, African and Asian countries, as well as the United States by cross-border flights
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The United Kingdom has reported community transmission of Ome Keron, with new infections doubling every two to three days
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The spike protein of the Omi Keron mutant strain contains a large number of mutations, which may increase the immune escape ability and/or spread of the mutant strain
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In fact, a recent study showed that compared with previously circulating strains, Omi Keron is more capable of infecting individuals during recovery
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Therefore, Omi Keron will quickly pose a threat to public health and may undermine the previous results achieved by the world in controlling the new crown pandemic
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However, the sensitivity of Omi Keron to antibody-mediated virus neutralization remains to be analyzed
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 The team of Stefan Pöhlmann from Georg-August-University Göttingen and the German Primate Center reported that the spike protein of the Omi Keron mutant escaped compared to the Delta mutant The efficiency of the antibody is 44 times higher, which will render the therapeutic antibody ineffective and may impair the protective effect of the antibody induced by a previous infection or two doses of Pfizer vaccine (BNT162b2)
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The new mRNA vaccine booster induces neutralizing immunity against Omi Keron mutant strains.
Highlights of the research highlights.
The spike protein of Omi Keron mutant strain contains 34 mutations, more than other mutant strains; two injections of mRNA vaccine against Omi Keron The neutralization effect of the three-injection mRNA vaccine can induce a strong cross-neutralization effect, which is effective against mutant strains including Omi Keron; Compared with other new crown mutants, Omi Keron pseudoviruses infect cells More efficient
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Research Introduction The Omi Keron variant (BA.
1/B.
1.
1.
529) of the new crown virus was first discovered in Botswana, Africa, and was reported to the World Health Organization in November 2021
.

Subsequently, Omi Keron infection cases increased rapidly in South Africa, and Omi Keron was designated by the World Health Organization (WHO) as a "variants of concern" (variants of concern)
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As a new mutant strain, Omi Keron contains a large number of previously discovered new mutations with immune escape potential, which is unprecedented
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The entire genome of this mutant strain contains 59 mutations, of which as many as 36 mutations occur in the spike protein, which is the medium through which the virus enters the host cell and is also the main target of neutralizing antibodies
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Studies on the mutations of previous new coronaviruses have shown that mutations in the receptor binding domain mediate the escape of vaccine-induced neutralizing antibodies, and in some cases enhance virus infectivity by increasing the affinity of the virus to ACE2
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The receptor binding domain of Omi Keron contains 15 mutations, some of which are the same as previous variants
.

For example, beta variants (B.
1.
351) and gamma variants (P.
1) contain K417, E484, and N501 residue mutations
.

Perhaps because the neutralizing antibody response is concentrated on a limited receptor binding domain epitope, these mutations can effectively reduce the neutralization induced by the vaccine
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In the United States, there are three vaccines that have been approved by the FDA or emergency use authorization (emergency use authorization).
All of these vaccines use the spike protein of the original wild-type new coronavirus as the only immunogen
.

The technical pathways of these vaccines include spike-encoding mRNA in lipid nanoparticles (BNT162b2 produced by Pfizer-BioNTech and mRNA1273 produced by Modena) or adenovirus vector vaccines (Ad26.
COV2.
S produced by Johnson & Johnson)
.

These new crown vaccines have been very successful in inducing and neutralizing humoral and cellular immunity
.

More importantly, it has reduced infections, hospitalizations and deaths caused by the new coronavirus during clinical trials and rapid global deployment
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However, it has been proven that the neutralizing antibody response and vaccine efficacy vary with vaccine preparations, decrease with the extension of time after vaccination, and are negatively affected by emerging virus mutations
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In response to the weakening of the antibody response and the emergence of new variants, the third shot of mRNA vaccine ("boost shot") has been approved for use in people who completed vaccination 6 months ago, and has been shown to be effective in inducing high school and antibody titers
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For people vaccinated with Johnson & Johnson adenovirus vaccine, it is recommended to cross vaccination with mRNA vaccine 2 months after the initial vaccination
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However, although previous studies have shown that the neutralizing effect of the vaccine on wild-type new coronaviruses can predict the effectiveness of the vaccine against mutant strains, it is still unclear whether this correlation will affect people who have been vaccinated with booster injections and those who are highly affected by Omi Keron.
Whether the mutant strain is still established
.

Previously, the team of Alejandro B.
Balazs from the Ragon Institute of MGH, MIT, and Harvard developed and verified a high-throughput pseudovirus neutralization assay to understand vaccines And the host characteristics of the immune difference between the new crown variant strain and other coronaviruses
.

In this article, the Alejandro B.
Balazs team used this detection method to test the neutralizing efficacy of the sera of 239 individuals against wild-type, delta mutant and Omi Keron mutant pseudoviruses
.

These people have been fully vaccinated with one of the three vaccines approved in the United States-Pfizer mRNA vaccine, Modena mRNA vaccine or Johnson & Johnson adenovirus vaccine, including 70 vaccines that followed cross-vaccination or mRNA booster after the initial vaccination.
Vaccination program, people who have received the third dose of mRNA vaccine
.

It is worth noting that the Alejandro B.
Balazs team found that all three basic vaccination programs have no or low neutralization effects on the Omi Keron mutant strain
.

Individuals who received the third dose of mRNA vaccine showed a strong neutralizing effect on Omi Keron, despite their neutralizing titers against wild-type virus and individuals who received only two doses of vaccine ("no booster injection") Similar
.

In addition, in vitro infection experiments have shown that Omi Keron pseudovirus still relies on human ACE2 receptors to enter target cells, and its efficiency in infecting target cells is four times higher than that of wild-type pseudovirus and twice as high as that of Delta mutant pseudovirus
.

In summary, the results of the Alejandro B.
Balazs team show that under the current vaccination plan, the Omi Keron variant can escape the vaccine-induced neutralizing immunity and is more infectious than the previous variant
.

Nevertheless, the researchers found that individuals receiving the third dose of mRNA vaccine have strong cross-neutralizing immunity to Omi Keron, which indicates that existing vaccines can overcome the escape of humoral immunity from "mutants that need attention" in the future
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Review: Cell science editor Yang Yang.
The original text of the relevant paper information was published in Cell, a journal of Cell Press,