Written By: Dewanshee Ingale, BPharm
In a landmark move, the FDA has granted approval to Moderna’s mNEXSPIKE, marking a new chapter in COVID-19 vaccine evolution. Approved on May 30, 2025, was a historic landmark towards the continuous development and evolution of messenger RNA (mRNA) technology based vaccines. The vaccine is such created that it acts as a next generation booster to improve the COVID-19 protection primarily focusing on the high-risk people. High risk populations include older adults from the age of 65 and above as well as smaller adults from the age of 12-24 with serious medical conditions defined by the Centres’ for Disease Control and Prevention (CDC) and that can increases the worsening of the outcomes if they are infected by virus. With the grand approval, Moderna now expects to provide mNEXSPIKE in addition to its original Spikevax® vaccine during this upcoming 2025-2026 respiratory virus season.
Present data and background
COVID-19 still serves as a major public health risk in the world. In 2024, the virus took more than 47,000 lives in America, which translates to a death every 11 minutes. Older adults usually experience very severe sickness, hospitalization, and death as compared to other groups. CDC surveillance data from October 2023 to April 2024 show that this older age group represented 70% of adult hospitalizations. Adults aged 65 and older comprised approximately 70% of all COVID-19-related hospitalizations among adults in the U.S. Among the adults who died in the hospital due to COVID-19, 80% were aged 65 and above.
The high prevalence of certain medical conditions further compounds this vulnerability. For example, obesity may increase the risk of severe COVID-19 outcomes by 1.4 times, diabetes by 1.8 times, and chronic lung diseases by as much as 3.2 times. These conditions significantly raise the likelihood of serious health complications. This data underscores the urgent need for effective and targeted vaccination strategies such as Moderna’s next-generation mNEXSPIKE vaccine to protect those most at risk, especially as the COVID-19 virus continues to evolve.
mNEXSPIKE is built upon Moderna’s mRNA-1273 (Spikevax) platform, but with an updated design, which primarily focusing on the key regions of the SARS-CoV-2 spike protein instead of targeting the whole structure. This invention, when combined with a lower dose (10 µg vs. Spikevax’s 50 µg), aims to improve efficiency while reducing reactogenicity. The development of mNEXSPIKE was guided by real-time data and advancements in prognostic analytics, reflecting Moderna’s commitment to continuous innovation and optimization.
A Novel Approach
Moderna’s mNEXSPIKE characterizes an important step ahead in COVID-19 vaccine. It is created on the basic foundation of mRNA technology but is designed in such a way that it is more efficient and can address present and future challenges as compared to previously present COVID-19 vaccines. mNEXSPIKE offers an enhanced mRNA technique that targets the specific region of the SARS-CoV-2 spike protein. This enables the human’s immune system to react strongly while it delivers a significantly low dose at 10 micrograms, which is one-fifth of the dose of Moderna’s original Spikevax vaccine.
The lowered-dose formulation is not only responsible for reducing the side effects but also for rationalizing manufacturing and distribution. mNEXSPIKE can be stored at regular refrigerator temperatures (2-8°C) for 90 days, overcoming the logistical difficulties of the prior existing mRNA vaccines and enabling use in a wide geographic area, particularly in areas where the facility of cold storage does not exist.
Individuals who have already received the COVID-19 vaccine are advised to use this vaccine as a booster vaccine to protect adults 65 years and above or 12-64 years old with other comorbidities. Clinical trials have established that this new vaccine offers more protection or equivalent protection in comparison to the previously existing vaccine. A stronger immune response is elicited against both the Omicron subvariants and the original virus strain.
With a designed antigen, reduced doses, and improved storage stability, mNEXSPIKE bears a very clever strategy for pandemic protection. This leads to increased efficiency, adaptability, and patient friendliness for those who are at risk.
Clinical trials and approval
Rigorous clinical trial data support the FDA approval of Moderna’s mNEXSPIKE COVID-19 vaccine, which represents efficacy and safety in different populations. The efficacy and safety of mNEXSPIKE were evaluated in a randomized, active-controlled NextCOVE clinical trial (NCT05815498) that was conducted in the United States, the United Kingdom, and Canada. The conducted large-scale evaluation included 11,417 individuals who were aged 12 years and above, with a median follow-up of 8.8 months.
The study population was distinct, with an average age of 56 years (range: 12-96 years). Demographically, the trial included
8.7% adolescents (12-17 years)
62.6% of adults (18-64 years)
28.7% older adults (65+ years)
The NextCOVE trial enrolled participants who were evenly divided between the mNEXSPIKE group (n = 5,706) and the comparator vaccine group (n = 5,711). Nearly all participants had received at least one prior COVID-19 vaccine dose, with an average interval of 9.8 months since their most recent vaccination. Notably, 74.3% of participants showed evidence of prior SARS-CoV-2 infection at baseline.
The mNEXSPIKE vaccine used in the study was a bivalent formulation, delivering a 10 microgram total dose comprising 5 µg targeting the original SARS-CoV-2 (Wuhan strain) and 5 µg targeting the Omicron variant. This represents a substantial dose reduction compared to the 50 µg dosage of the comparator vaccine. Participants received a single 0.2 mL intramuscular injection, administered at least three months after their previous COVID-19 vaccine dose.
Results
The primary endpoint of the NextCOVE Phase 3 trial (NCT05815498) was to evaluate the efficacy of Moderna’s mNEXSPIKE (mRNA-1283) vaccine in preventing symptomatic COVID-19, starting 14 days after a single booster dose, compared to the existing Spikevax (mRNA-1273) vaccine. The study enrolled over 11,400 participants aged 12 years and older, with nearly all having received at least one prior COVID-19 vaccination. The results demonstrated that mNEXSPIKE met the criteria for non-inferiority to Spikevax and showed a relative vaccine efficacy (rVE) of 9.3% in preventing symptomatic COVID-19 across all adults. Notably, in adults aged 65 and older, mNEXSPIKE showed an even higher rVE of 13.5%, indicating stronger protection in this high-risk group. The vaccine was also well tolerated, with a safety and reactogenicity profile comparable to or slightly improved over Spikevax, despite using a significantly lower dose of just 10 µg (versus 50 µg for Spikevax).
Safety profile
Moderna’s mNEXSPIKE has established a favorable safety profile across all age groups, with most side effects being mild to moderate and transient. Commonly reported adverse reactions included pain at the injection site, fatigue, headache, muscle pain, joint pain, chills, and nausea or vomiting, with slightly lower frequencies observed in adults aged 65 and older.
A key safety consideration is the rare risk of myocarditis and pericarditis, particularly in males aged 12–24 years, typically occurring within one week of vaccination. The estimated rates are approximately 8 cases per million doses in recipients under 64 years and 25 per million in males aged 12–25.
The vaccine is contraindicated in individuals with a history of severe allergic reactions (e.g., anaphylaxis) to any mNEXSPIKE component or prior Moderna COVID-19 vaccine dose. Syncope may also occur post-vaccination, as seen with other injectables.
Overall, the safety profile of mNEXSPIKE is consistent with other mRNA vaccines, and combined with its 9.3% higher relative vaccine efficacy, especially in older adults, it is a strong candidate for protecting high-risk populations during the ongoing COVID-19 threat.
Impact and future viewpoint
The sanction of Moderna’s mNEXSPIKE COVID-19 vaccine demonstrates an important invention in the pandemic protection, particularly for high risk groups like elderly people and those who have comorbidities. mNEXSPIKE offers an improved efficiency at a reduced dose and storage requirements, and is expected to increase the accessibility of vaccines and uptake, usually in areas with limited cold storage requirements. The vaccine’s improved safety and effectiveness characteristics are likely to reduce the total number of hospitalizations and deaths caused the COVID-19 which has taken thousands of lives in the U.S. over a year.
Looking at the future, mNEXSPIKE has undoubtedly set an entirely new standard for the upcoming next-generation vaccines, showcasing the potential for design and innovation that can protect the vulnerable population better. The approval also depicts the transformation toward personalized and adaptable vaccine planning strategies, which are of utmost importance due to the continuous evolution of the virus.
Overall, the newly created booster vaccine, Moderna’s mNEXSPIKE, is not only capable of strengthening the present pandemic preparedness but also lays the way for future innovation in mRNA vaccine technology and protection of public health.
References
mNEXSPIKE FDA Approval History https://www.drugs.com/history/mnexspike.html
Introducing mNEXSPIKE: Moderna’s New COVID-19 Vaccine https://www.modernatx.com/media-center/all-media/blogs/introducing-mnexspike-modernas-new-covid-19-vaccine
Moderna Receives U.S. FDA Approval for COVID-19 Vaccine mNEXSPIKE https://investors.modernatx.com/news/news-details/2025/Moderna-Receives-U-S–FDA-Approval-for-COVID-19-Vaccine-mNEXSPIKE/default.aspx
FDA approves Moderna’s new COVID-19 vaccine https://www.cidrap.umn.edu/covid-19/fda-approves-modernas-new-covid-19-vaccine
FDA Package Insert – MNEXSPIKE https://www.fda.gov/media/186738/download
Spyros Chalkias, Antionette Pragalos, Adebayo Akinsola, et al, Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain and N-Terminal Domain mRNA Vaccine, The Journal of Infectious Diseases, Volume 231, Issue 4, 15 April 2025, Pages e754–e763, https://doi.org/10.1093/infdis/jiaf022
A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 (NextCOVE), moderna clinical trials, https://trials.modernatx.com/study/?id=mRNA-1283-P301&Latitude=27.6648274&Longitude=-81.5157535&LocationName=Florida,%20USA&MileRadius=100
The article is reviewed and fact-checked by the editorial team of Pharmacally.com
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