Omicron a ‘significant challenge’ to two-dose vaccination

Jolyon Attwooll

15/12/2021 4:57:46 PM

Research suggests the new variant of concern is easily the most adept yet at avoiding antibodies and that ‘significant community spread’ is expected, including among the fully vaccinated.

Graph showing fold reduction in neutralisation.
The fold reduction in neutralisation is far greater than has been seen in any other previously identified coronavirus variant.

Scientists have underlined the pivotal role of boosters in protecting against Omicron, as evidence crystallises on the variant’s ability to evade antibodies produced through a primary vaccination course.
In a media briefing held on Wednesday morning, experts from the UNSW’s Kirby Institute outlined laboratory results that confirm the variant’s dramatically advanced capacity to cause breakthrough infections.
Associate Professor Stuart Turville of the institute’s Immunovirology and Pathogenesis Program described how work showed Omicron’s enhanced ability to avoid neutralising antibodies.
He is the corresponding author of a pre-print paper which reports a 17–22-fold reduction in neutralisation titres in laboratory tests.
‘Neither vaccination with two doses of AstraZeneca nor Pfizer were able to stimulate an antibody response strong enough to neutralise Omicron in our assays among the samples we tested,’ Associate Professor Turville said.
‘This is significant and supports the need for boosters to protect from infection.’
As a result, Associate Professor Turville’s study states that Omicron represents ‘a significant challenge to the existing two dose vaccination strategy’ adopted by many countries around the world.
The study’s findings were derived from tests carried out using a laboratory-grown Omicron sample and serum from a range of individuals, including the fully vaccinated, those who had recovered from COVID-19, and patients who had previously had the virus and then subsequently been vaccinated.
Omicron proved significantly more adept at avoiding antibodies than any previous variant of concern, he said.  
Moreover, the significantly enhanced ability of the variant of concern to evade antibodies happened ‘irrespective of the vaccine’ used in a primary two-dose course, or whether the patient had previously had the virus.
‘They are all the same with Omicron,’ he said.
Omicron set to overtake Delta
When asked whether Omicron is likely to dominate in Australia, as is already happening in South Africa and the UK, Associate Professor Turville said he believes it is set replace Delta.
‘It looks to be, based on the numbers,’ he told reporters. ‘It’s accelerating’.
The briefing happened as NSW Health reported the biggest ever jump in case numbers for the state; there were 1360 cases recorded until 8pm on 14 December, 556 more than the previous day. 
The figures coincided with a planned lifting of several COVID-19 restrictions in the state, including the removal of a mask mandate except on public transport and in airports, and the lifting of density limits.
According to Professor Adrian Esterman, Chair of Biostatistics and Epidemiology at the University of South Australia, the effective reproduction number (Reff) has now increased to 1.78. He predicts NSW case numbers will shortly overtake Victoria.

On Wednesday NSW Health Minister Brad Hazzard said recent modelling is now suggesting 25,000 cases a day will be likely by the end of January.
Dr Tedros Adhanom Ghebreyesus, the Director-General of the World Health Organization (WHO) also issued a warning about the transmissibility of the new variant.
‘Omicron is spreading at a rate we have not seen with any previous variant,’ Dr Ghebreyesus tweeted on Wednesday.
‘I need to be very clear: vaccines alone will not get any country out of this crisis. It’s not vaccines instead of masks, distancing, ventilation or hand hygiene. Do it all. Do it consistently. Do it well.’
Severe disease and boosters
While evidence on the virulence of COVID-19 caused by Omicron is still emerging, vaccines do appear to offer more protection against severe disease than infection, believes Dr Deborah Cromer, the group leader in infection epidemiology and policy analytics at the Kirby Institute.
‘What we see there is that whilst there is very limited protection against symptomatic infection ... from Omicron from the primary vaccination, there is still some protection against severe disease and hospitalisation afforded from those vaccines,’ she said.
The paper also suggests that a booster is likely to give a significant increase in protection against both symptoms and severe disease.
It estimates vaccine efficacy against symptomatic disease at 74.4% following an mRNA booster, and 95.7% against severe disease, compared to 37.2% and 78.8% respectively without a booster. The paper does acknowledge, however, limited current data and ‘a lack of understanding of baseline severity with Omicron’.
‘Having a booster shot with a mRNA vaccine massively increases neutralising antibodies and results in protection at really quite high levels,’ Dr Cromer said.
Omicron is also likely to increase the need for regular boosters, she believes; however, that prediction comes with the caveat that it will depend on the dominant variant.
‘About a month ago, we would have said that we wouldn’t need a booster in another six months’ time, we might wait for a year or two,’ Dr Cromer said.
‘Now we are seeing that after a booster shot we are getting high immunity but that is at the level that it will wane within another six months.’
Real-world studies
While the study has produced some worrying findings, Kirby Institute Director Professor Anthony Kelleher said even though neutralisation in the lab is important, it is very different to prevention of infection and disease in the real world.
‘Studies like this are important parts in understanding the Omicron puzzle, but it will be some time before we know exactly what this will mean in clinical practice,’ he said.
‘Other levels of immunity such as immune memory in T cells still need to be considered in terms of protection from severe disease.
‘As observed with many other variants, the vaccine response may not fully protect people from becoming infected, but importantly, it will reduce the chance of developing severe disease.’
However, a new real-world study from South Africa released this week also indicates that the efficacy of the Pfizer vaccine has declined significantly since the emergence of Omicron.
The analysis, conducted by South Africa’s largest private health insurance administrator, Discovery Health, reports that vaccine efficacy for avoiding hospitalisation has dipped to 70%, down from 93% during the Delta wave. Associate Professor Turville said the results corresponded with what he has observed in the laboratory.
‘What we have estimated is tracking pretty close to what is happening in the real world, so our assays our running well,’ he said.
‘What we have got is a pretty good early warning system for things like this.’
COVID-19 treatments
Associate Professor Turville’s paper, ‘SARS-CoV-2 Omicron: evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern’ includes concerning findings for the treatment of COVID-19.
It reports a much-reduced impact for monoclonal antibody therapies, with only Sotrovimab demonstrating encouraging laboratory results against Omicron.
‘Although the retention of neutralising activity by Sotrovimab against Omicron is promising, the complete loss of activity of many other monoclonals remains a concern,’ the study reads.
‘The development of new and improved monoclonal antibody modalities is urgently warranted.’
Booster gap
Professor Kelleher told reporters that the Australian Technical Advisory Group on Immunisation (ATAGI) will be carefully scrutinising whether to change current guidelines on boosters.
‘This sort of data – in conjunction with the epidemiological data about rates of infection and rates of disease severity in people that are vaccinated – and triangulating that with ... modelling data, will give us an answer about the ideal time for boosting,’ he said.
‘I am sure they will be looking at the data as it accumulates over the ensuing weeks to inform their policy on boosting.’
Last week ATAGI reduced the minimum gap between primary vaccination and booster doses to five months.
The pre-print study suggests that more targeted vaccines will likely be needed in future.
‘Whilst boosters utilising the same Clade A Spike may increase antibody titres to Omicron, development of variant specific boosters may be more pragmatic in the longer term if Omicron persists,’ the authors write.
‘The latter will be very important in those groups that may have a limited titre, such as in the elderly or immunocompromised.’
Associate Professor Turville told reporters there is still much to be established about Omicron and advised a cautious approach while scientific understanding is evolving.
‘This is an unknown and it is doing things that are different,’ he said. ‘And I think we have just got to be careful.’
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