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Monoclonal antibodies neutralize all SARS-CoV-2 variants of concern

Researchers in Canada and the United States have identified a monoclonal antibody that strongly neutralizes a variant of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). This is the drug that causes the ongoing coronavirus disease 2019 (COVIdD-19) pandemic.

“LY-CoV1404 is a potent SARS-CoV-2 binding antibody that neutralizes all known variants of concern,” said AbCellera Biologics Inc of Vancouver. Bryan Barnhar said.

Researchers have shown that some of the existing therapeutic antibodies have shown reduced efficacy against certain mutants, and the effects of these mutants on vaccine efficacy are not yet fully understood. Given that, it warns that new mutant resistance treatments are “urgently needed.”

The team states that the wide range of mutant binding and strong neutralizing activity observed in LY-CoV1404 supports clinical development and rapid deployment to support the fight against current and new mutants. I am.

The preprinted version of the research treatise is bioRxiv* Servers and articles have been peer reviewed.

New variants can slow the pace and success of vaccination

The new SARS-CoV-2 mutant may alter the trajectory of the COVID-19 pandemic as it may evade and reduce vaccination-induced immunity. Effectiveness of Antibody-based treatment.

Numerous studies have demonstrated the safety and efficacy of antibody-based therapies and their potential to reduce the economic and healthcare burden during a pandemic. These treatments can be readily available to vulnerable groups, such as those with immunodeficiency and those over the age of 65.

However, in order for antibody therapy to remain effective, they must retain strong neutralizing activity against SARS-CoV-2 mutants that carry ongoing mutations.

“High neutralization may also offer lower clinical doses and the opportunity to explore alternative routes of administration,” writes Barnhar and colleagues.

Studies have shown that specific mutations in mutants such as the B.1351 mutant that emerged in South Africa and the P.1 strain that occurred in Brazil have the binding affinity of antibodies that are currently being tested or have already been approved. It has been consistently shown that it can reduce. Emergency use.

Therefore, antibodies that retain binding and neutralizing activity in the presence of these mutations would be a very valuable tool, Barnhar et al.

What did the researchers do?

The team performed a high-throughput screening of peripheral blood mononuclear cells isolated from COVID-19 convalescent donors approximately 60 days after onset of symptoms.

This screening identified an immunoglobulin G1 (IgG1) monoclonal antibody that targets the receptor-binding domain of SARS-CoV-2. Spike protein It blocks the binding of spikes to the host cell receptor angiotensin converting enzyme 2 (ACE2).

To Pseudovirus Studies have shown that an antibody called LY-CoV1404 is against all currently known variants, including B.1.351 South African strains, P.1 Brazilian strains, B.1.1.7 (UK) variants, and B. Showed a very strong neutralizing activity. .1.427 / B.1.429 (California) variant, and B.1.526 (New York) variant.

The team discovered that LY-CoV1404 directly competes with the monoclonal antibodies S309 and REGN10987 for spike RBD binding. Barnhar et al. State that this exhibits a different binding epitope than other ACE2-blocking antibodies, such as the emergency-licensed monoclonal antibodies gamlanivimab and etesebimab.

Structural analysis of LY-CoV1404 that binds to RBD. Tertiary structure of the Fab portion of LY-CoV1404 bound to the peplomer receptor binding domain.

Structural analysis of LY-CoV1404 that binds to RBD. Tertiary structure of the Fab portion of LY-CoV1404 bound to the peplomer receptor binding domain.

LY-CoV1404 epitope is highly conserved

Further analysis revealed that the RBD positions that make up the LY-CoV1404 epitope are highly conserved except for N439 and N501. However, antibody binding and neutralizing activity was unaffected by the most commonly occurring mutations at these positions (N439K and N501Y).

“LY-CoV1404 binds to different epitopes that have been found to be widely circulating within newly emerging mutations, including mutations that reduce vaccine efficacy,” the team wrote. ..

In addition, antibody-peplomer interactions were found to be caused by amino acids that rarely mutate in the Global GISAID (Global Initiative for Avian Influenza Data Sharing) EpiCoV database, with LY-CoV1404 reducing severe COVID-19 and mortality. I will.

Antibodies are less likely to be affected by future mutations

Researchers have found that LY-CoV1404 is likely to be very effective against current mutants, as well as future mutations due to the low level of changes previously observed in its binding epitopes. It is said that it is not easily affected by.

“The unique binding epitope of LY-CoV1404, along with the infrequent mutations observed within this epitope, provides a highly effective solution for the spread of known mutants by this antibody, the current VOC and new As an important complementary approach to vaccination, Barnhar et al. Conclude that it has the potential to provide potent treatments for these mutants.

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.

Monoclonal antibodies neutralize all SARS-CoV-2 variants of concern

Source link Monoclonal antibodies neutralize all SARS-CoV-2 variants of concern

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