- The genome of the Omicron variant has a large number of mutations, including more than 30 in the spike protein.
- This has raised concerns about the effectiveness of monoclonal antibody treatments that target the spike protein.
- A new study has found that most antibody treatments against the Omicron variant were less effective than against previous variants.
- Antiviral drugs remdesivir and molnupiravir retained their effectiveness over the Omicron variant, as did an intravenous (IV) drug candidate Pfizer is testing.
The large number of mutations carried by the omicron variant raises concerns about the effectiveness of antiviral drugs and antibody treatments.
A new labStudy found that most antibody treatments are less effective against the Omicron variant than against the previous variants. These results support beforehand studies who came to similar conclusions.
Notably, the three antiviral drugs, all of which were approved by the Food and Drug Administration (FDA), retained their effectiveness over Omicron.
The results of this study appear as correspondence in Das New England Journal of Medicine.
Monoclonal antibodies are synthesized in the laboratory and mimic antibodies that the immune system makes. Similar to antibodies produced by the immune system, monoclonal antibodies bind to the virus and prevent it from infecting human cells.
Treatment with monoclonal antibodies in the early stages of SARS-CoV-2 infection can be significantly reduced the risk of hospitalization and death and has been an invaluable tool in treating those at high risk of COVID-19.
Monoclonal antibodies used to treat COVID-19 typically target the SARS-CoV-2 spike protein, which plays a crucial role in mediating the virus’ entry into human cells.
Mutations in the gene encoding the spike protein can alter the structure of the protein. Such mutations can subsequently alter the ability of monoclonal antibodies to bind to the spike protein and neutralize the virus.
The omicron variant has at least 33 mutations in the spike protein. Because of this, scientists were concerned about whether antibody treatments would retain their effectiveness against the new variant.
To assess the effectiveness of monoclonal antibodies against Omicron, the scientists used a laboratory test to compare the ability of different antibody treatments to neutralize Omicron and previous SARS-CoV-2 variants.
Researchers evaluated how well a live virus infects cells in laboratory cultures in the presence of a specific monoclonal antibody.
They evaluated the neutralizing ability of seven different monoclonal antibodies against the alpha, beta, gamma, delta and omicron variants.
For each monoclonal antibody, the researchers determined the antibody concentration required to reduce by half the ability of a particular variant to infect the cells.
Although most antibodies were effective against the earlier variants, all monoclonal antibodies tested in the study showed a reduced ability to neutralize Omicron.
For example, the Regeneron monoclonal antibody Casirivimab effectively neutralized gamma and beta, but 18- to 75-fold higher concentrations of the antibody were required to neutralize Omicron.
The GlaxoSmithKline antibody Sotrovimab was superior to other antibodies in neutralizing Omicron, requiring lower concentrations to inhibit it. Still, the concentrations of the drug that were able to neutralize the Omicron variant were three times higher than those of the Delta or Beta variants.
Medical news today spoke with Dr. Stuart Turville, Virologist at the University of New South Wales, Sydney. He explained why sotrovimab may have performed better than casirivimab:
“While many developed antibodies have great potency over previous variants, changes in the spike glycoprotein rendered them ineffective. Sotrovimab binds to a conserved site that persists in omicron, so its activity is largely retained.”
Similar to monoclonal antibody treatments, the currently approved COVID-19 vaccines are designed to elicit an immune response against the wild-type SARS-CoV-2 spike protein.
In accordance with the results of the present study, other studies have shown one Reject in the levels of neutralizing antibodies against Omicron in subjects who received two doses of the mRNA vaccine.
These antibodies are important to prevent and at least partially explain SARS-CoV-2 infection higher Number of breakthrough infections with the Omicron variant.
In addition to using single monoclonal antibodies, doctors have used cocktails of two or more antibodies to treat COVID-19. In the present study, the researchers examined the effectiveness of three such antibody combinations.
Of the three, the AstraZeneca antibody combination Evusheld was the most effective at blocking Omicron’s ability to infect cultured cells. However, the concentrations of antibody combination that the Omicron variant was able to neutralize were 24 to 142 times higher than the previous variants.
The other two antibody combinations failed to neutralize Omicron.
Incidentally, the reduced effectiveness of these two antibody combinations – manufactured by Eli Lilly and Regeneron Pharmaceuticals – has led to this FDA to discontinue the use of these drugs for COVID-19 caused by Omicron.
Next, the researchers assessed whether the high number of genetic mutations dampened the effectiveness of currently used antiviral drugs against Omicron.
These antivirals included remdesivir and molnupiravir, both of which inhibit the key enzyme required to make copies of the SARS-CoV-2 genome. Researchers also tested an IV version of a Pfizer drug candidate that inhibits a SARS-CoV-2 enzyme required for cleaving viral proteins during replication.
IV drug use is a method of delivering drugs into a vein and directly into the bloodstream.
The study authors tested these drugs because Omicron has a single mutation in each of the two enzymes targeted by these antivirals.
They found that all three drugs were just as effective against Omicron as they were against the earlier variants. However, the researchers warn that these results from laboratory experiments need to be verified in clinical trials.
MNT spoke with DR. Rajesh Gandhi, infectious disease physician at Massachusetts General Hospital and professor of medicine at Harvard Medical School in Boston. dr Gandhi, who was not involved in the study, said:
“These data are consistent with the results of several other studies. The laboratory studies show that the activity of several anti-SARS-CoV-2 monoclonal antibodies (casirivimab/imdevimab, bamlanivimab/etesevimab) is significantly reduced compared to Omicron. In contrast, sotrovimab, another approved anti-SARS-CoV-2 monoclonal antibody, remains active against Omicron in these laboratory studies.”
“Besides, the two are oral [COVID-19] Drugs – paxlovid and molnupiravir – and the [IV] Drug remdesivir are active against Omicron in these laboratory studies.”
“The results of this study,” concluded Dr. Gandhi, “support the recommendations to use one of the following four drugs for inpatients with COVID-19 who are at high risk [of] Progression: paxlovid, sotrovimab, remdesivir and, if unavailable, molnupiravir.”
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