Promising Results for Next-Generation Vaccine
Moderna has announced promising results from new pre-clinical and human studies of its next-generation COVID-19 vaccine, mNEXSPIKE, showing a strong immune response against the rapidly spreading SARS-CoV-2 LP.8.1 sublineage. According to the company, the updated vaccine induced a more than 16-fold increase in neutralizing antibodies among individuals aged 12 and older.
The findings were based on postmarketing clinical trials of the 2025–26 formulation of mNEXSPIKE, which specifically targets the LP.8.1 strain. For comparison, Moderna’s first-generation mRNA vaccine Spikevax demonstrated an eight-fold increase in LP.8.1-neutralizing antibodies in the same age groups, highlighting the stronger response generated by the updated formulation.
FDA Authorization and Ongoing Trials
In August, the U.S. Food and Drug Administration (FDA) authorized the new mNEXSPIKE formula for individuals aged 12 to 64 with at least one underlying health condition, as well as for all adults aged 65 and older. These groups are considered at higher risk of developing severe COVID-19, making the updated shot a key tool in seasonal protection.
To meet its postmarketing obligations to the FDA, Moderna is currently conducting multiple trials. These include a single-arm phase 3b/4 study in the authorized age groups and a placebo-controlled phase 4 trial in adults aged 50 to 64 without high-risk conditions. The FDA’s approval decision was largely based on preclinical evidence, though questions had initially been raised earlier in 2025 about whether more human trials would be required before updated COVID-19 vaccines could be authorized.
Navigating the Regulatory Landscape
That uncertainty stemmed from an April statement by the Department of Health and Human Services (HHS), which suggested that all new vaccines—including COVID-19—would need to undergo placebo-controlled safety testing prior to licensing. At the time, it was unclear whether seasonal vaccines such as flu and COVID shots would be exempt from these requirements.
Moderna’s press release reaffirmed that the most recent clinical evidence supports earlier preclinical data, validating the FDA’s decision to approve the LP.8.1-adapted mNEXSPIKE vaccine. The company also reported that the safety profile of the vaccine in ongoing postmarketing studies remains consistent with previous research, indicating no new safety concerns.
Evolving Standards for Vaccine Coadministration
Meanwhile, the broader regulatory landscape continues to evolve. Although the updated flu and COVID vaccines have entered the market without major regulatory delays, FDA officials have suggested that new standards for vaccine coadministration may soon be implemented. Vinay Prasad, the FDA’s top vaccine official, has indicated that before manufacturers recommend administering COVID-19 vaccines alongside flu or other vaccines, they may need to conduct randomized, controlled clinical trials with clinical disease outcomes as the primary endpoint.
The FDA has already applied this position to a recent decision memo regarding Pfizer and BioNTech’s updated COVID-19 vaccine, Comirnaty. In that case, the agency emphasized that any claims about coadministration or optimal vaccine sequencing would require additional controlled trial data.
Conclusion: A Critical Tool for Public Health
With the emergence of new SARS-CoV-2 strains and the ongoing need for seasonal boosters, Moderna’s latest findings suggest that mNEXSPIKE could become a critical next-generation vaccine for protecting vulnerable populations. The FDA’s cautious but flexible approach highlights the balance regulators must strike between rapid public health responses and ensuring long-term vaccine safety and efficacy.
Moderna now faces the task of proving how well the 16× antibody boost will translate into real-world protection, especially against severe disease and hospitalization. As immunologic titers wane over time, Moderna may need to plan booster strategies or variant updates more frequently. The company will also need to prepare payers, public health systems, and global markets for potential scale-up of mNEXSPIKE. Availability in low- and middle-income countries will be critical, and Moderna may leverage existing mRNA distribution partnerships to accelerate access.
