A recently published Phase 4 head-to-head trial has evaluated the tolerability of Sanofi’s Nuvaxovid (recombinant protein technology) against Moderna’s mNexspike (next-generation mRNA technology). The study focused primarily on patient experience and post-vaccination side effects rather than efficacy.
Key empirical findings The double-blind study involving 1,000 adult participants in the U.S. revealed that the protein-based vaccine exhibited significantly fewer side effects across all pre-specified endpoints:
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Systemic reactions: 84% of Nuvaxovid recipients experienced at least one systemic reaction within seven days, compared to 92% in the mRNA group.
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Severity levels: Severe side effects such as fatigue, headache, or fever that disrupted daily activities were reported by less than 10% of the Nuvaxovid group, whereas the rate was 20% for mNexspike.
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Injection site symptoms: Pain, redness, and swelling were over 75% more frequent among those who received Moderna’s shot.
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Duration and intensity: Symptomatic reactions associated with Nuvaxovid were found to be both milder and of shorter duration.
Implications for vaccination strategy Based on these results, nearly twice as many participants expressed a preference for the same vaccine type for the following year due to better tolerability. Health experts noted that the patient experience is a crucial factor in determining whether individuals return for routine annual protection. Reducing reactogenicity could significantly impact and improve vaccination uptake, particularly among those who avoid shots due to potential side effects.
Market context
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Nuvaxovid (Sanofi/Novavax): Following a deal exceeding $1 billion with Novavax, Sanofi has taken over the marketing of this traditional protein-based alternative in Europe and the U.S.
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mNexspike (Moderna): This next-gen mRNA vaccine was approved for seniors and high-risk groups in May 2025 after demonstrating improvements over its predecessor, Spikevax.