Staying power: does Moderna’s vaccine have edge on Pfizer?

Moderna’s Covid-19 vaccine may offer longer-lasting protection than Pfizer’s, new research suggests, as governments and scientists debate who needs booster shots and when. 

Recent studies show the Moderna jab prompts a stronger immune response than the rival mRNA vaccine from BioNTech/Pfizer, and that its effects wane more slowly. 

Paul Burton, Moderna’s chief medical officer, said a stream of “extremely reassuring” studies in the past few weeks showed Moderna’s shot had “long-lived” efficacy, stood up to the Delta variant and could even help people with compromised immune systems. 

Research published this week in the Journal of the American Medical Association found that Belgian healthcare workers given the Moderna jab had more than double the number of antibodies two months after their second dose than those receiving Pfizer’s.

Higher antibody levels soon after vaccination should lead to longer-term protection and greater resistance to Covid variants, according to Deborah Steensels, one of the study’s authors. While the scientists were only able to count all antibodies, not the gold standard neutralising antibodies, she said the correlation was strong enough to bolster the theory.

“The efficacy of protecting people from severe disease and mortality is high for all vaccines and that’s the main goal of vaccines,” she said. “But our hypothesis is that for the duration of protection against mild disease to last longer, you need higher antibody titres after vaccination.” 

Another study this week from the University of Virginia found recipients of the Moderna jab had more antibodies than those given Pfizer’s, with the difference more marked in older people. The findings echo those of a draft paper last month by University of Toronto researchers assessing immune responses among long-term care facility residents.

Some scientists suggest the Moderna jab could last longer because its dose of mRNA — the genetic code that teaches the immune system how to recognise the coronavirus’s spike protein — is three times higher than Pfizer’s. Another factor may be the time between doses, at a recommended four weeks for Moderna but three weeks for Pfizer.

Eric Topol, director of the Scripps Research Translational Institute, said Covid vaccines all appeared to be more effective in countries with longer gaps — such as the UK and Canada — than in the US and Israel, which stuck to the schedule from the jabs’ phase 3 trials. 

“I think the rush to get the trials done . . . has accentuated the waning,” he said. 

Pfizer said its vaccine continued to be “highly efficacious”, including in tackling variants and preventing severe disease and hospitalisation. 

The antibody studies lend weight to other yet to be peer-reviewed “preprint” papers that show more breakthrough infections among people vaccinated with Pfizer’s jab than with Moderna’s.

Research from the Mayo Clinic in the US and Qatar showed a better efficacy rate for the Moderna vaccine, although the results are complicated by the fact the Pfizer shot has often been distributed earlier so may have had more time to wane or been given to the more vulnerable. 

These studies show sharper declines in efficacy as the Delta variant emerged. But earlier research following up on the phase 3 trials showed a similar pattern: Pfizer’s efficacy declined to a low to mid 80 per cent rate against symptomatic infection after four to six months, against Moderna’s 93 per cent after five to six months. 

Other vaccines may also have greater longevity than Pfizer’s, with two studies suggesting the Oxford/AstraZeneca jab’s efficacy wanes more slowly than Pfizer’s, albeit from a lower initial rate. 

Oxford researchers, not associated with the university’s vaccine development and using data from the UK’s Office for National Statistics, found the Pfizer jab’s efficacy against symptomatic infection almost halved over four months, while AstraZeneca’s protection declined far more slowly. 

The pattern is backed up by data published last week from the Zoe symptom study app. Pfizer’s efficacy fell 14 percentage points to 74 per cent in five to six months, while AstraZeneca’s fell 10 per percentage points to 67 per cent after four or five months. 

Scientists say this could be because the adenovirus that delivers the Oxford vaccine endures in the body for longer than mRNA, giving the immune system more time to respond. Johnson & Johnson, which also uses an adenovirus, said neutralising antibodies in people given its single-shot jab were actually higher eight months after vaccination than 29 days after. 

“We thought Pfizer was the bee’s knees but it might be wearing off slightly faster,” said Tim Spector, Zoe co-founder and a professor at King’s College London. 

But he cautioned that we did not yet have the hard evidence to differentiate between vaccines, with the crucial data coming in the next six months. 

Paul Hunter, an infectious disease expert at the University of East Anglia, warned about relying too heavily on studies that could just be “random fluke”. “These sort of unexpected findings do crop up quite regularly in epidemiology,” he said.

All the studies use so-called “real world evidence”, collected outside of trial conditions. John Moore, a virologist at Cornell University, said the key question was whether the populations receiving each vaccine were comparable because local factors such as who is prioritised for each vaccine can confound the outcomes. 

“Is it a true apples-to-apples comparison or is there an orange or two creeping in there?” he said. “Nothing we’ve seen so far should mean any difference in boosting policy for the two mRNA vaccines.” 

Investors are not yet pricing in the vaccines’ differences in an unusual market where politicians hold the purse strings and doses are still in short supply.

Moderna and Pfizer’s plans for boosters are still moving in lockstep, with both companies developing vaccines tailored to the Delta variant, in case they become necessary, and submitting data on a third dose to the US Food and Drug Administration in recent weeks. 

Third jabs enhance antibody levels. Pfizer said people given a booster at least six months after the second dose had 5 to 10 times more antibodies than after the initial two doses. Moderna submitted its data on Wednesday, saying an extra half dose of its vaccine, which still has more mRNA than Pfizer’s, resulted in antibody levels “significantly above” what had been found in the initial trial and held up to variants including Delta. 

A vaccine that needs to be readministered more often could be a boon for investors, providing a regular revenue stream — a potential conflict of interest that made some scientists cautious about the company’s initial push for boosters. 

Scripps Research Translational Institute’s Topol said he found Pfizer’s initial push for booster shots “really grotesque”, as there did not appear to be evidence of the need for the extra jabs, which could make the company “billions of dollars”. But now, with more data coming out of Israel, he believes they will be required at least for the over 60s. 

Jo Walton, an analyst at Credit Suisse, said it was too soon to conclude any significant differences in efficacy between the Covid-19 vaccines — and certainly too early to have any market implications. 

She believes governments are trying to secure as many doses as possible in the short term to juggle booster campaigns, potential programmes for vaccinating children and the threat of variants. 

“Governments have had zero choice: they have had to get whatever they can get their hands on with a reasonable visibility of supply,” she said. 

Jon Miller, an analyst at Evercore, said the vaccines’ differences had not been “convincingly demonstrated” and the “horse race” between Moderna, Pfizer and AstraZeneca was not driving their stock.

Instead, he said, investors were concerned about whether waning efficacy could lead to calls for lockdowns as Delta spreads and case numbers rise. “People are more worried about the aggregate durability of vaccines full stop.”