Moderna’s New COVID Vaccine Outperforms Current Shot in Key Adult Trial

Moderna announced on Thursday that its latest COVID-19 vaccine demonstrated higher efficacy in adults during a Phase III trial compared to its current Spikevax vaccine. Spikevax, an mRNA-based vaccine, encodes a full-length SARS-CoV-2 S protein and showed 94.5% efficacy in its pivotal 2020 trial. Despite this, real-world usage indicated potential improvements, particularly against emerging variants and logistics simplification. Moderna's new mRNA-1283 vaccine aims to address these aspects.

Unlike the Spikevax, mRNA-1283 encodes two segments of the S protein crucial for neutralizing SARS-CoV-2. These segments are the N-terminal domain and the receptor binding domain. Jacqueline Miller, Moderna’s senior vice president of infectious disease development, elaborated on the vaccine's design during the company's vaccine day in March 2024. She emphasized that the most effective antibodies target these domains, suggesting that this could enhance combination vaccines by reducing interference, thereby providing a more competitive product.

In March, Moderna reported that mRNA-1283 elicited a stronger immune response than Spikevax in a Phase III trial. The recent update highlights how this improved immune response has translated into better protection against COVID-19. The investigational vaccine's efficacy was non-inferior to Spikevax across a diverse population, including 11,400 participants aged 12 and above, and it surpassed the first-generation vaccine's efficacy in adults. A significant trend was observed in adults aged 65 and older, where the highest antibody titers were noted in March.

One of the notable advantages of mRNA-1283 is its efficacy at a lower dose. While Spikevax is administered at 50μg, mRNA-1283 achieves similar or superior results at just 10μg. Moderna attributes this to the shorter mRNA length of mRNA-1283, which leads to higher protein expression levels even at lower doses. Additionally, the design of mRNA-1283 might allow for extended storage under refrigeration.

The safety profile of mRNA-1283 was comparable to Spikevax in the latest study, with common side effects including injection site pain, fatigue, headache, and muscle aches. Moderna intends to discuss the future steps for this program with regulatory authorities.

This update follows closely on the heels of Moderna's Phase III data release on its combined COVID-19 and influenza vaccine. The combined vaccine incorporates the next-generation COVID-19 vaccine, reflecting Moderna's findings that the adapted antigen results in less interference. The combination vaccine showed superior immune responses against both COVID-19 and influenza compared to currently licensed products.

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