head-to-head comparison reveals how they stack up

A table at a vaccination center covered in many different colored kidney dishes containing different kinds of COVID-19 vaccine

Pick one: a mass-vaccination center in Leipzig, Germany, offers the COVID-19 vaccines made by Moderna (red dish), Pfizer–BioNTech (green) and AstraZeneca (yellow).Credit: Jens Schlueter/Getty

A rare head-to-head comparison shows that the COVID-19 vaccines made by Pfizer and Moderna outperform those from Johnson & Johnson and Novavax1. The data also provide a finely detailed picture of the immune protection that each vaccine offers — information that could be useful for designing future vaccines.

The research was posted on the preprint server bioRxiv on 21 March. It has not yet been peer reviewed.

The study assessed the 4 vaccines using 14 metrics, including levels of several types of immune cell such as T cells and B cells, as well as immune molecules called neutralizing antibodies. Such investigations are sorely needed to sort through the flood of COVID-19 vaccines in the research pipeline and on the market, researchers say.

“It’s a really nice analysis by premier immunologists that builds upon what has been previously shown,” says Robert Seder, an immunologist at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

Previous comparisons of COVID-19 vaccines have often brought together data from different studies, which might have been conducted with slightly varying laboratory techniques. For the latest study, by contrast, researchers applied the same techniques across all the vaccines they investigated.

“When you try to compare [vaccine data] between different papers, which is what many of us have been doing for over a year now, you get apples to oranges comparisons, and you can be way off,” says Shane Crotty, an immunologist at La Jolla Institute for Immunology in California and a co-author of the preprint.

The four vaccines that Crotty and his co-authors examined fall into three classes. The jabs made by Moderna in Cambridge, Massachusetts, and by Pfizer in New York City and BioNTech in Mainz, Germany, are both based on messenger RNA. Johnson & Johnson (J&J) of New Brunswick, New Jersey, has produced a ‘viral vector’ vaccine that uses a harmless virus to deliver SARS-CoV-2 genetic material into host cells. The vaccine made by Novavax in Gaithersburg, Maryland, contains pieces of the SARS-CoV-2 spike protein.

Strengths and weaknesses

Antibody levels induced by two doses of Pfizer’s or Moderna’s mRNA vaccine tended to wane substantially over six months. By contrast, antibody levels from J&J’s one-shot vaccine were stable or even increased over time. But antibody levels measured six months after vaccination with the J&J jab were still lower than those observed six months after vaccination with an mRNA vaccine.

Novavax’s two-shot regimen induced antibody responses on a par with those to the mRNA vaccines. However, after the Novavax jab, levels of CD8+ T cells, which destroy infected cells, were low to undetectable, whereas the other three vaccines performed well in this metric.

These results generally support the findings of previous studies. But the latest research offers a more extensive analysis of the immune system’s response than do earlier studies, and uses an apples-to-apples approach.

No losers

“This is not meant to proclaim winners and losers,” says study co-author Alessandro Sette, an immunologist at La Jolla. Instead, the study is meant to “provide a comprehensive evaluation of the different variables”, he says.

Novavax has received authorization for its vaccine in 38 countries. The vaccines made by Moderna, Pfizer and J&J have all received wide authorization globally.

One caveat is that the study looked at the effects of the Novavax jab in only 12 people. He examined the other three vaccines in 30 volunteers each.

Seder notes that the analysis considers the effects of only a two-dose regimen of the mRNA vaccines. It does not consider the protection provided by boosters, because the authors began the work in late 2020, before a third shot was recommended by health authorities. Crotty, Sette and their colleagues are now conducting a similar head-to-head study that includes mRNA boosters.

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