In short
Single-stranded 5'-capped mRNA encoding the N-terminal domain and receptor-binding domain of the viral spike protein of SARS-CoV-2 (XBB.1.5) is an investigational mRNA vaccine component being studied for the prevention of COVID-19. One authorised Phase 3 trial is currently evaluating this substance as part of a combination vaccine against both SARS-CoV-2 infection and influenza infection in adults aged 65 years and older, with a planned enrollment of 410,000 participants.
Key points
- One Phase 3 trial is authorised to study this mRNA vaccine component for preventing COVID-19 and influenza in adults aged 65 and older.
- The trial plans to enroll 410,000 participants, making it one of the largest vaccine effectiveness studies in this population.
- The primary outcomes measure medically attended influenza and/or COVID-19 and hospitalization from either infection.
- The substance is part of an investigational combination vaccine (mCombriax, mRNA-1083) that targets both SARS-CoV-2 and influenza viruses.
- The trial compares the combination vaccine against separate co-administration of high-dose influenza vaccine and a COVID-19 mRNA vaccine.
- The trial status is Authorised, meaning it has received regulatory approval to begin enrolling participants.
What is single-stranded 5'-capped mRNA?
Single-stranded 5'-capped mRNA encoding the N-terminal domain and receptor-binding domain of the viral spike protein of SARS-CoV-2 (XBB.1.5) is an investigational messenger RNA (mRNA) vaccine component. It carries the genetic instructions for cells to produce specific parts of the SARS-CoV-2 spike protein, specifically the N-terminal domain and the receptor-binding domain. The XBB.1.5 designation refers to the Omicron subvariant of SARS-CoV-2 that this mRNA sequence is designed to target.
In the authorised trial, this substance is being studied as part of an investigational combination vaccine called mCombriax (also known as mRNA-1083), which is designed to protect against both COVID-19 and influenza in a single injection. The substance is not yet authorised as a standalone medicine; it is an investigational vaccine component under evaluation in clinical research.
How does single-stranded 5'-capped mRNA work?
This mRNA vaccine component works by delivering genetic instructions into cells. Once inside the cell, the mRNA instructs the cell's protein-making machinery to produce fragments of the SARS-CoV-2 spike protein — specifically the N-terminal domain and the receptor-binding domain. The immune system then recognises these protein fragments as foreign and develops an immune response against them, preparing the body to defend against future exposure to the actual virus.
The 5'-cap structure is a chemical modification at one end of the mRNA molecule that helps stabilise it and allows it to be read efficiently by the cell's protein-making machinery. This design feature is common to mRNA vaccines and helps ensure that the genetic instructions remain intact long enough to produce the desired immune response.
Which conditions is it used or studied for?
- SARS-CoV-2 infection (COVID-19) — the trial is evaluating whether this mRNA component, as part of a combination vaccine, can prevent medically attended COVID-19 and COVID-19 hospitalization in older adults.
- Influenza infection — the same combination vaccine is also being tested for its ability to prevent medically attended influenza and influenza hospitalization.
How is single-stranded 5'-capped mRNA given?
In the authorised trial, this mRNA component is administered as part of the mCombriax combination vaccine, which is given by intramuscular injection. The trial record describes mCombriax as a dispersion for injection in a pre-filled syringe. The intervention listing indicates a dose of 1 milligram, though this represents the total combination vaccine dose rather than the mRNA component alone.
For comparison, the trial also includes separate arms where participants receive either the Spikevax JN.1 COVID-19 mRNA vaccine (50 micrograms) or the Efluelda Tetra high-dose influenza vaccine, both also given by intramuscular injection.
What do the clinical trials show?
How is the trial designed?
The single authorised trial (trial identifier 2026-526720-49-00) is a Phase 3, pragmatic, randomised trial comparing the mCombriax combination vaccine against same-day co-administration of the active comparators — the high-dose influenza vaccine Efluelda and the COVID-19 mRNA vaccine Spikevax (mRNA-1273) — in adults aged 65 years and older.
The trial has a planned enrollment of 410,000 participants, making it a very large study designed to evaluate vaccine effectiveness under real-world conditions. The status is Authorised, meaning the trial has received regulatory approval and is preparing to enroll participants.
What is the trial measuring?
The primary endpoints of the study are the occurrence of two outcomes: medically attended influenza and/or COVID-19, and influenza and/or COVID-19 hospitalization. These outcomes will be compared between participants receiving the combination vaccine and those receiving separate co-administration of the two individual vaccines.
Who can take part in the trial?
The trial is open to adults aged 65 years and older. This age group is a key population for both influenza and COVID-19 vaccination because older adults are at higher risk of severe illness, hospitalization, and complications from these infections.