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FrontierVaccines & clinical trialsWorking brief

Vaccines & clinical trials

What changed in Moderna’s vaccine?

A closer look at mNEXSPIKE: a redesigned antigen, a lower mRNA dose and the trial behind its first US approval.

“Next generation” is a claim worth unpacking. With mNEXSPIKE, start with what the RNA tells a cell to make.

A different antigen

mNEXSPIKE’s mRNA encodes the N-terminal and receptor-binding domains of the SARS-CoV-2 spike, linked to a membrane anchor. The pivotal trial compared 10 micrograms of the new vaccine with 50 micrograms of Moderna’s earlier bivalent vaccine. Both trial formulations targeted the same viral lineages.

FDA review · Antigen design and trial

Read the result, not just the headline

The trial met its prespecified noninferiority criterion for preventing symptomatic COVID-19. The FDA reported 9.3% relative vaccine efficacy, with a 99.4% confidence interval from −6.6% to 22.8%. That interval crosses zero: this analysis did not establish superior clinical efficacy. It also does not mean 9.3 percentage points more absolute protection.

FDA review · Efficacy analysis, Table 8

Where the story goes next

  • What does the antigen redesign make possible for dose, durability and manufacturing?
  • How do antibody measurements relate to clinical outcomes, particularly severe disease?
  • How do the original trial formulations relate to later seasonal updates and the people eligible to receive them?

This working brief examines the evidence behind the May 2025 US approval. It is not a review of the current seasonal formulation.

Editorial preview · Coverage in development

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