Researchers puzzle over suggestions that jabs do not stop transmission as well as first thought.
A rise in vaccinated people becoming infected with coronavirus has cast doubt over the lasting efficacy of Covid-19 vaccines, according to new studies, including one that found protection gained from the BioNTech/Pfizer shot declined more rapidly than that from the AstraZeneca jab.
An Oxford university study published on Thursday found that the efficacy of the Pfizer vaccine against symptomatic infection almost halved after four months, and that vaccinated people infected with the more infectious Delta variant had as high viral loads as the unvaccinated.
Two research papers from the US and Qatar have also fuelled debate over the need for top-up booster shots as they found higher numbers of "breakthrough infections" than anticipated, even though protection against serious cases of the virus appears to hold.
Natalie Dean, a biostatistics professor at Emory University, said the spread of the Delta variant had made it "a lot harder" to stop transmission.
"The situation has changed with respect to how far we think vaccines can take us," she said. "We've been brought back to a more modest — but still critical — goal: to prevent severe disease, hospitalisations and deaths."
What do the latest studies show?
The Oxford scientists showed vaccine efficacy falling since the Delta strain became dominant in the UK in May. While the Pfizer shot was more effective at first, by four to five months after the second dose its efficacy was roughly the same as AstraZeneca's jab, as the protection offered by the latter has barely budged.
The paper's authors were not involved in the creation of the AstraZeneca vaccine, which originated at Oxford university.
Tomas Hanke, professor of vaccine immunology at Oxford's Jenner Institute, speculated that the AstraZeneca shot generates longer-lasting immunity because its spike protein sticks around for more time, promoting a bigger immune response.
"When you deliver RNA, like the Pfizer vaccine, you deliver a finite number of mRNA molecules which are eventually cleared from the system," he said. "But when you deliver the adenovirus, as AstraZeneca does, you deliver a template which then keeps producing these mRNAs that then produce the spike protein, so there's no ceiling."
A preprint based on evidence collected at the Mayo Clinic hospital chain in the US state of Minnesota showed protection against infection fell from 91 per cent to 76 per cent between February and July for the vaccine made by Moderna, and from 89 per cent to 42 per cent for the Pfizer jab.
It is unclear how much of this was a result of the Delta variant, which was absent in Minnesota in February but dominant by July, and how much was owing to waning immunity as the months passed after people were inoculated.
A separate Qatar study focusing on the Delta variant found that two doses of Pfizer were 60 per cent effective at stopping infection, whether symptomatic or not, while Moderna was 86 per cent effective.
How does this compare to what we knew already?
Public Health England's real-world studies in May painted a rosier picture: a double Pfizer vaccination was 88 per cent effective at preventing symptomatic infection with the Delta variant. Studies in Canada and Scotland put efficacy at 87 per cent and 79 per cent, respectively.
But the new studies appear more in line with research in Israel, which found the Pfizer jab was just 41 per cent effective at preventing symptomatic infection in June and July. The Oxford study was the first to suggest that the efficacy of the Pfizer shot may be waning faster than AstraZeneca's.
Making direct comparisons between the different studies is difficult, however. The US and Qatari papers included people who did not develop symptoms — which is known to produce lower estimates for efficacy.
Yet Laith Abu-Raddad, an author of the Qatar paper and a professor at Weill Cornell Medicine, part of Cornell University, said the results were "quite surprising" because scientists had been more concerned about efficacy against the Beta variant rather than Delta strain.
Is this the waning of immunity over time?
It could be that declining efficacy is caused by waning immunity, supporting the argument for a third shot. Studies have shown antibody levels decline over time although scientists have not identified the level where they stop being protective. Other parts of the immune system, such as the harder-to-monitor T-cells, also play a role in fighting the virus.
Abu-Raddad said his study suggested waning immunity but cautioned that the "sky is not falling", given that vaccines still prevent severe illness.
Koen Pouwels, lead author of the Oxford study, said they had taken into account a "long list" of complicating factors, so it was reasonable to assume the decline was because of waning immunity.
Pfizer has said for some time that a third shot would be necessary, probably about eight to 10 months after the second dose. It has applied to several regulators for approval for a booster shot.
Adam Finn, a member of the UK's joint committee on vaccination and immunisation, said there was "no clear evidence" of the need for a booster and urged caution, especially when some companies had a "strong financial incentive to propose boosting".
Does the Moderna vaccine offer more protection against Delta?
The studies also appeared to show that the Moderna vaccine may be more effective at tackling the Delta variant than the Pfizer jab.
In the Minnesota study, Pfizer's efficacy against infection dropped much more sharply as the Delta variant rapidly replaced Alpha as the dominant strain. One complication is that the Pfizer jabs were given first and Moderna's rollout has been more recent, but the researchers tried to compensate for this by only comparing groups vaccinated in the same month.
The Oxford researchers only had enough data to study the impact of the first dose of Moderna but found it enjoyed efficacy similar to or greater than a single shot of the other vaccines.
The Qatar study showed a far lower efficacy rate for the Pfizer jab but it did not adjust for how long each individual had been vaccinated. However, Abu-Raddad said he did not believe that could be the sole explanation.
"Both are really great vaccines but it might be a difference related to the dose," he said. Moderna's vaccine has more than three times the mRNA — the genetic instructions that teach the body to recognise the spike protein — than the Pfizer jab.
Are these studies game-changing?
Experts have been reluctant to draw dramatic conclusions from these new studies because there are so many other variables.
People who were vaccinated early tended to be more vulnerable, so they might have been less likely to have robust immune responses anyway.
"How old you are, the underlying risk factors that predict that you had the vaccine a long time ago could also be the reason behind the vaccines failing and you getting sick," Professor Finn said.
Muge Cevik, an infectious disease researcher at St Andrews University in Scotland, said it would be increasingly challenging to interpret such studies owing to complicating factors including changing behaviour, such as after the lifting of lockdowns, or immunity developed in the wake of infection.
Even without these shifts muddying the waters, it is possible that vaccines may be less effective simply because over time, vaccinated people come into contact with the virus again and again.
"The more transmission you have, the more likely it is that you get a breakthrough case," said Yaniv Erlich, a computational geneticist. "Someone rolls the dice once, twice, three times and maybe the third time they roll the wrong number and get [infected]."
Written by: Hannah Kuchler and John Burn-Murdoch
© The Times of London