CureVac COVID Vaccine Let-down Spotlights mRNA Design Challenges

4, describes it as the “best platform for antibody and neutralization levels”. In light of the new CureVac data, many scientists who spoke to Nature agree.

“Modified mRNA has won this game,” says Rein Verbeke, an mRNA-vaccine researcher at Ghent University in Belgium.

There are a few other possible explanations for CureVac’s tolerability problems. Structural differences in the non-coding regions of the CureVac sequence could play a part. Alternatively, the higher storage temperature of CureVac’s jab might have accelerated the breakdown of mRNA in the vial, yielding pieces of genetic code that would raise immune hackles. And if any impurities were introduced during the company’s manufacturing process, these would, in principle, have the same effect.

So for some scientists it remains too early to draw conclusions. “The jury is still out on which of these is a better technology,” says Jeffrey Ulmer, a former pharmaceutical executive who now consults on vaccine research issues. He predicts that both modified and unmodified mRNA will be useful in different contexts. “It could be that there’s not a one-size-fits-all solution to everything.”

CureVac hopes that its vaccine — or at least its unmodified mRNA technology — might yet deliver. The company is continuing its trial and expects a final analysis in the next few weeks. On a public health level, even if the vaccine fails, “I don’t think it’s going to set the world back much”, says Jacob Kirkegaard, a vaccine-supply expert at the Peterson Institute for International Economics, a think-tank in Washington DC.

He points out that another second-generation vaccine that offers many of the same logistical selling points as CureVac’s, such as long-term refrigerator storage, has stood up to the variant challenge well. Earlier this week, Novavax in Gaithersburg, Maryland, reported that its protein-based vaccine was more than 90% effective at preventing COVID-19 in a large US trial, run at a time that the Alpha variant was prevalent.

The scale of production of other vaccines more than makes up for the lack of CureVac’s product, Kirkegaard says.

CureVac, in collaboration with London-based GlaxoSmithKline, also has a second-generation COVID-19 vaccine in the works that, like its predecessor, uses unmodified mRNA, but has been fine-tuned so that it elicits levels of neutralizing antibodies that are around ten times higher, according to data from rat and monkey studies. “Our optimization has never stopped,” says CureVac’s chief technology officer Mariola Fotin-Mleczek. “It’s too early to say unmodified, natural messenger RNA is not an option.” Human trials are due to launch later this year.

This article is reproduced with permission and was first published on June 18 2021.