Moderna stakes a claim against Covid-19’s Delta variant

Just weeks after a huge UK dataset confirmed the real-world efficacy of Pfizer/Biontech's and Astrazeneca’s vaccines against hospitalisation due to the Covid-19 Delta variant, a US analysis of the Mayo Clinic’s health records has backed Moderna’s shot – and then some.

While repeated studies have supported all the major vaccines’ ability to cut hospitalisations, the Mayo Clinic data suggest that, purely in terms of breakthrough Delta variant infections, Moderna’s Spikevax is twice as effective as Pfizer/Biontech’s Comirnaty. This is a fact that many bulls will cling to as Moderna’s valuation continues to defy gravity.

It should be stressed that the Mayo Clinic data are not peer-reviewed, and have only been published on the Medrxiv preprint server. A separate analysis of health data from Qatar, also only in preprint form so far, also gives Spikevax an edge over Comirnaty against the Delta variant, though there are caveats here.

Delta dominance

The Mayo Clinic analysis concerns Minnesota in January to July, an important period in one key regard: the Alpha, or UK, Covid-19 variant was fairly dominant until the end of May, but by July it had almost completely been supplanted by Delta, also known as the India variant.

The researchers analysed several hundred thousand PCR-tested patients, and whittled these down to three groups of around 26,000 each, matched for crucial baseline characteristics. The three groups comprised unvaccinated individuals, those who had had two doses of Spikevax, and those who had been fully vaccinated with Comirnaty.

Across the seven-month period Spikevax slightly outperforms Comirnaty in straight vaccine efficacy and efficacy against hospitalisation. But the gap widens when comparing May against July, with Comirnaty’s efficacy against symptomatic Covid-19 falling from 83% to just 42%, while Spikevax’s drops less drastically, from 93% to 76%.

While this clearly seems to favour Spikevax, it should again be stressed that both vaccines retained significant protection against hospitalisation during July, at 75-81%, a decline from May of just 12-14 points. Likewise, in the earlier UK analysis Comirnaty and Astra’s Vaxzevria showed continuing efficacy against hospitalisation due to the Delta variant.

Still, the Mayo paper researchers separately compared other US states in their database, including Florida, which has seen a coronavirus surge. This found that the risk of breakthrough infection was cut by 50% in those fully immunised with Spikevax versus those double-vaccinated with Comirnaty.

The separate Qatar preprint concerns a matched March-July dataset of Spikevax or Comirnaty vaccinated individuals, 1,810 of whom developed Delta variant Covid-19, and 760,983 of whom remained Covid-19-free by PCR.

This, too, numerically backs Spikevax over Comirnaty, a fact that will please Moderna bulls. But a curious aspect is that Comirnaty’s efficacy appears to fall for double versus single-vaccinated individuals, from 64% to 54% in the unadjusted dataset, or from 66% to 60% adjusting for sex, age and other factors.

Spikevax’s efficacy rises from single to double vaccination, and the authors stress that Comirnaty’s effectiveness against the Delta variant is “statistically similar” comparing one against two doses. Instead, they suggest Comirnaty’s protective effect waning over time, something not seen with Spikevax in this analysis.

Still, there are caveats. Qatar, in common with Israel and the US, used a short dose interval, meaning that patients in the Qatar analysis had received their second Comirnaty dose longer ago than those in the UK and Canada, where efficacy is running at 75%. And the easing of restrictions has differed for vaccinated versus unvaccinated Qataris.

Either way, the two preprints suggest differences emerging between two mRNA-based vaccines that had until now been viewed as pretty similar. The Mayo analysis authors note that each Spikevax dose provides three times more Spike protein mRNA copies than Comirnaty, something they suggest could more effectively prime the immune response.

A third study of Covid-19 variants of concern, published yesterday in Science, found Spikevax to elicit antibodies persisting for six months. However, it is still unclear how important for ongoing protection antibody levels are versus T-cell responses, and yesterday the FDA authorised a third dose of Spikevax or Comirnaty for immunocompromised people.