Discovery of Omicron Neutralizing Antibodies Could Lead to Effective Treatments for COVID-19 Variants
| By HospiMedica International staff writers Posted on 29 Dec 2021 |
An international team of scientists have identified antibodies that neutralize Omicron and other SARS-CoV-2 variants, raising hopes of the findings leading to the development of more effective vaccines and antibody treatments for COVID-19 variants.
In a research project supported by the Howard Hughes Medical Institute (Chevy Chase, MD, USA), researchers identified the antibodies which target areas of the virus spike protein that remain essentially unchanged as the viruses mutate. By identifying the targets of these “broadly neutralizing” antibodies on the spike protein, it might be possible to design vaccines and antibody treatments that will be effective against not only the Omicron variant but other variants that may emerge in the future.
The Omicron variant has 37 mutations in the spike protein, which it uses to latch onto and invade cells. This is an unusually high number of mutations. It is thought that these changes explain in part why the variant has been able to spread so rapidly, to infect people who have been vaccinated and to re-infect those who have previously been infected. The researchers speculate that Omicron's large number of mutations might have accumulated during a prolonged infection in someone with a weakened immune system or by the virus jumping from humans to an animal species and back again.
To assess the effect of these mutations, the researchers engineered a disabled, non-replicating virus, called a pseudovirus, to produce spike proteins on its surface, as coronaviruses do. They then created pseudoviruses that had spike proteins with the Omicron mutations and those found on the earliest variants identified in the pandemic. The researchers first looked to see how well the different versions of the spike protein were able to bind to protein on the surface of cells that the virus uses to latch onto and enter the cell. This protein is called the angiotensin converting enzyme-2 (ACE2) receptor. They found the Omicron variant spike protein was able to bind 2.4 times better than spike protein found in the virus isolated at the very beginning of the pandemic.
The researchers then looked at how well antibodies against earlier isolates of the virus protected against the Omicron variant. They did this by using antibodies from patients who had previously been infected with earlier versions of the virus, vaccinated against earlier strains of the virus, or had been infected and then vaccinated. They found that antibodies from people who had been infected by earlier strains and from those who had received one of the six most-used vaccines currently available all had reduced ability to block infection. Antibodies from people who had previously been infected and those who had received the Sputnik V or Sinopharm vaccines as well as a single dose of Johnson & Johnson had little or no ability to block – or “neutralize” – the Omicron variant's entry into cells. Antibodies from people who had received two doses of the Moderna, Pfizer/BioNTech, and AstraZeneca vaccines retained some neutralizing activity, albeit reduced by 20- to 40-fold, much more than any other variants.
Antibodies from people who had been infected, recovered, and then had two doses of vaccine also had reduced activity, but the reduction was less, about fivefold, clearly demonstrating that vaccination after infection is useful. Antibodies from people, in this case a group of renal dialysis patients, who had received a booster with a third dose of the mRNA vaccines produced by Moderna and Pfizer/BioNTech showed only a 4-fold reduction in neutralizing activity. All but one antibody treatments currently authorized or approved to be used with patients exposed to the virus, had no or had markedly reduced activity against Omicron in the laboratory. The exception was an antibody called sotrovimab, which had a two- to three-fold reduction of neutralizing activity, the study found.
But when they tested a larger panel of antibodies that have been generated against earlier versions of the virus, the researchers identified four classes of antibodies that retained their ability to neutralize Omicron. Members of each of these classes target one of four specific areas of the spike protein present in not only SARS-CoV-2 variants but also a group of related coronaviruses, called sarbecoviruses. These sites on the protein may persist because they play an essential function that the protein would lose if they mutated. Such areas are called “conserved.” The finding that antibodies are able to neutralize via recognition of conserved areas in so many different variants of the virus suggests that designing vaccines and antibody treatments that target these regions could be effective against a broad spectrum of variants that emerge through mutation.
“This finding tells us that by focusing on antibodies that target these highly conserved sites on the spike protein, there is a way to overcome the virus’ continual evolution,” said David Veesler, investigator with the Howard Hughes Medical Institute and associate professor of biochemistry at the University of Washington School of Medicine in Seattle.
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JIMMY NSUBUGA
Shoppers pass a Covid vaccination centre in Solihull town centre. (PA)
A scientist has said every person will likely catch Covid more than once during their lifetime.
Professor Francois Balloux, a geneticist from University College London (UCL), warned although vaccines perform well against severe disease, hospitalisation and death, the jabs were “meh” against stopping infections.
He added this meant most people would likely catch coronavirus soon and then again at least once.
But the professor was criticised for having “no empathy” after making the remarks on Twitter on Monday.
Prof Balloux wrote: “This is not an easy message to convey, even to those who have already accepted that zero-covid was toast.
"Essentially everyone will eventually get infected by SARS-CoV-2 in the near future, and likely more than once in their lifetime."
He said measures like wearing masks would prolong the pandemic by delaying some getting infected.
Prof Balloux added: "Vaccine protection against infection is meh, though protection against severe symptoms, hospitalisation and death remains stellar (~20x), including against Omicron."
He said the virus would become endemic, continuing: “I believe it is time to give in soon.
“Vaccine protection rates are as high as they may ever be in many places, and now we've got a couple of decent drugs.
“Pretending we remain in control, of sorts, is just becoming too costly.”
Dr Simon Ashworth, head of speciality and consultant intensive care medicine at Imperial College Healthcare NHS Trust, criticised Prof Balloux for his comments.
He replied: “If you lie down on the tracks and wait the train to run you over, then it will run you over. So get up.
“Balloux has been consistently wrong about the pandemic… he sounds plausible but seems to have zero real understanding and no empathy.”
Prof Balloux later clarified he was not calling for restrictions to be lifted right now but suggested we continue controlling Covid case numbers over the coming months with proactive and reactive measures to ensure a smooth transition into the endemic.
Professor Francois Balloux said vaccines were “meh” against stopping infections. (Getty)
Earlier this month, chief scientific adviser Sir Patrick Vallance said the country was going through a “bumpy transition” from the coronavirus pandemic to it becoming endemic after the Omicron variant emerged.
He said: “What we are on is a road from pandemic to endemic, where this becomes a more regular infection like flu or something over time.”
Health Secretary Sajid Javid told MPs Covid variants would continue to develop for “many years”.
He said: “There are going to be variants of Covid, as he says, for many years and indeed there have been many hundreds of variants, and there is no country in the world that is better on the surveillance of those variants.”
Professor Mike Tildesley, a member of the Scientific Pandemic Influenza Modelling group (Spi-M), previously said repeated vaccinations could be offered “for years to come” to keep Covid at bay.
He told Sky News: “In the longer term, Covid is likely to become endemic and we probably are going to have to manage it with repeated vaccination campaigns for years to come.”
"It was 'futile' to try and predict when the pandemic will end"
The new and highly transmissible Omicron variant of the deadly coronavirus has increased immune escape compared with the Delta variant and appears likely to become the dominant SARS-CoV-2 strain globally in 2022, according to Singapore-based experts.
The World Health Organization (WHO) has called for the world to pull together to end the COVID-19 pandemic next year.
"2022 must be the year we end the pandemic," WHO Director-General Tedros Adhanom Ghebreyesus said in Geneva on Monday.
But Singapore-based experts said much depends on how potent the Omicron variant is and asserted that it was “futile” to try and predict when the pandemic will end.
“It appears likely that Omicron will become the dominant SARS-CoV-2 strain globally in 2022,” Public health expert Associate Professor Natasha Howard said, adding that the Omicron variant is more transmissible and has “increased immune escape” compared with the Delta strain.
The rise of the more transmissible variant, increased case numbers and hospitalisations are likely, said Howard, the interdisciplinary health policy and systems researcher from the Saw Swee Hock School of Public Health in Singapore.
“The implications of this are still unclear, but it shows that the pandemic is not controlled yet and until initial and booster COVID-19 vaccine doses are accessible to everyone eligible globally, we can expect new variants to emerge,” she warned.
For the Singapore population, it is clear that two COVID-19 vaccine doses are not enough to provide reasonable protection against Omicron and people should get booster shots as soon as they are eligible, she said.
Citing Imperial College modelling data, she said that the risk of reinfection with the Omicron variant is more than five times higher and it does not appear milder than the Delta variant.
Omicron will likely be the cause of a “significant wave” of COVID-19, said Associate Professor Ashley St John from the Duke-NUS Medical School’s Emerging Infectious Diseases Programme. "But while the Omicron variant is more transmissible than most we have seen, it is still SARS-CoV-2," she said.
“The genetic backbone of Omicron is very, very different … However, we don’t yet have consistent data whether those genetic differences result in increased severity,” the professor explained.
Public health experts are thus monitoring the data on severity for Omicron and are waiting for more concrete numbers to bolster the initial assessment that vaccines are efficacious against it, she said.
Dr Lim Wee Kiat, associate director at the Singapore Management University’s Centre for Management Practice, said it was “futile” to try and predict when the pandemic will end.
After all, the 1918 flu pandemic never really ended, according to the US CDC (Centre of Disease Control and Prevention), descendants of the influenza virus from more than a century ago still circulate today, Lim Wee said.
“The path to normalcy is going to be punctuated by twists and dead ends, even reversals, as we have seen here in Singapore and elsewhere,” the Channel quoted Dr Lim, a disaster sociologist by training, as saying.
And while Omicron may further delay the roll-out of the Singapore government’s COVID-19 endemic roadmap, the city state’s experience in managing the pandemic over the past two years is a plus.
“Our experience in managing the pandemic over the past two years means that we are unlikely to revert to a ‘circuit-breaker’ type situation, which will only serve as a last resort given Singapore’s endemic goal, especially since most of the population has been vaccinated,” said Nydia Ngiow, Singapore managing director of strategic advisory firm Bowyer Group Asia.
Meanwhile, Singapore reported 322 new COVID-19 cases on Thursday, of which 89 are imported or those who arrived here. There are also two fatalities, taking the country's death toll from coronavirus complications to 820 deaths.
As of Thursday, Singapore has recorded 277,042 COVID-19 cases since the start of the pandemic.
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