Pandemic protection: How will Covid vaccines fare against Omicron variant?

There is no conclusive evidence yet on how immune response holds up against the heavily mutated strain

The warning from the head of pharmaceuticals group Moderna that Covid-19 vaccines were likely to be less effective against the Omicron variant has provoked anxiety over the best weapon the world has to fight the pandemic.

Although the boss of vaccine developer BioNTech offered reassurance that the fully inoculated would have a “high level of protection against severe disease” from the new strain, there is as yet no conclusive evidence on how immune protection holds up against the heavily mutated variant.

Scientists who had not even heard of Omicron a week ago are racing to stress-test the existing jabs, while preparing a new vaccine formula tailored to the emerging threat.

Why do scientists fear vaccines will become less effective?

All the Covid vaccines available are made to defend against the original strain of the Sars-CoV-2 virus, first discovered in Wuhan, China. Omicron marks such a step-change from its ancestor that scientists fear the immune response programmed by the original vaccines may no longer work as effectively.


Omicron, first detected in southern Africa, possesses an unprecedented 50 mutations, more than half of which are on the spike protein that allows the virus to bind to human cells.

“There has been an arms race between the evolution of our antibodies as they are exposed to vaccines and/or infection, and the virus as it tries to evade those antibodies,” said Paul Bieniasz, professor of retrovirology at Rockefeller University. “Omicron is the virus’s latest salvo in that genetic conflict.”

Bieniasz’s team this year created a synthesised spike protein with 20 mutations, many of which overlapped with Omicron’s changes, and discovered that the artificial variant “was nearly completely resistant” to the neutralising antibodies from prior infection or two shots of a messenger RNA vaccine, he said.

“I’m fairly confident in my prediction that it will be the most antibody-resistant variant that has yet arisen. What the magnitude of that resistance will be, we don’t know,” Bieniasz added.

However, Ugur Sahin, head of BioNTech, who developed the vaccine now produced by Pfizer, struck a more positive note. “We believe fully vaccinated individuals will still have a high level of protection against severe disease caused by Omicron,” he said.

How likely is it that vaccines will have to be reformulated?

After Stéphane Bancel, the head of Moderna, predicted there would be a “material drop” in the effectiveness of existing vaccines, he said his company was pushing ahead with new drugs that targeted the Omicron variant.

Eleanor Riley, professor of immunology and infectious disease at the University of Edinburgh, said Bancel “may well be right in terms of whether the existing vaccines are sufficient to prevent infection”.

But the impact on hospital admissions and death was likely to be much less severe, she said, since “immunity to severe disease is mediated by T-cells” that are “less susceptible” to mutations.

T-cells form part of the immune system’s memory banks, providing sustained protection against severe illness.

Roberto Burioni, professor of microbiology and virology at the Vita-Salute San Raffaele University, stressed it was “impossible to judge” the nature of the virus based on the sheer number of mutations. “With mutations, it’s not all a numbers game,” he said, adding that tests of vaccines against the new variants would take at least a week.

Penny Heaton, global head of vaccines for Johnson & Johnson, said her team had begun preparing for the variant as soon as they had secured data. She said they were seeking to establish whether the current shot still held up at the same time as starting to create a tweaked version.

“My team . . . has been studying all the gene sequences that have been coming in and looking at how best to design that and getting everything ready to go to develop and manufacture that vaccine,” she said.

How long will it take and what are the constraints?

BioNTech, together with Pfizer, said late last week that it moved “months ago” to adapt its existing vaccine in case of an “escape variant”, and that it would be in a position to deliver initial batches within 100 days.

Oksana Pyzik, a teaching fellow at University College London’s School of Pharmacy, said vaccine makers had been on a “war footing” against any new variants for some time.

“The longest part of all of this process is not just tweaking the vaccine platform, it’s the safety testing, data interpretation and ramping up supply,” said Pyzik.

The model for updating the Covid vaccine is similar to that used in influenza vaccines, which are reformulated each year without the need for human clinical trials.

Jacob Glanville, a computational immunologist and founder of US therapeutics company Centivax, made the point that the 100-day timeframe was “crazy fast” and could not be shortened much more.

It involved a strictly controlled biological process of synthesising the new vaccine, followed by ramping up production and safety testing. “There are steps in biology you just can’t speed up,” he said.

All the leading manufacturers “can rapidly turn around new Omicron vaccines and generate reagents for immunogenicity in a couple of months”, said John Bell, regius professor of medicine at Oxford university, who helped engineer the deal that led to the Oxford/AstraZeneca vaccine.

“Much will depend on the agility of regulators,” he added.

But supplies of a new vaccine are likely to be in high demand. Airfinity, a life sciences analytics company, said that in the best-case scenario six billion doses could be produced by October next year.

Where does that leave the booster programme?

The threat from the new variant has added urgency to western booster jab programmes, as countries, including the UK, stepped up efforts to maximise immunity ahead of winter.

Scientists stressed that third booster jabs were no less important now the Omicron variant had emerged.

“There’s nothing to lose with boosters,” said Burioni at the Vita-Salute San Raffaele University. “If Omicron does reduce the effectiveness of vaccines, you’d prefer for it to fall from the protection of three doses rather than just two.”

One ominous piece of real-world evidence did emerge on Tuesday, with a report that two Israeli doctors had become infected with the Omicron strain despite receiving three doses of the Pfizer vaccine. They have so far shown mild symptoms.

“How [Omicron] will fare against the spectrum of antibodies in people who have had boosters, we simply don’t know,” said Rockefeller University’s Bieniasz.

He argued that those who had been both vaccinated and infected had the “gold standard” of immune protection, adding that his research had shown “they had a remarkable collection of antibodies that could neutralise even our synthetic mutation”.

This offered hope that booster shot recipients or the vaccinated who had prior infection might retain a “sizeable degree of protection”, he added. – Copyright The Financial Times Limited 2021