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    How mRNA vaccines work

    An mRNA vaccine delivers a short-lived genetic message that cells use to make an antigen, training the immune system without using the pathogen itself.[1][2] Modified nucleosides and lipid nanoparticles made the approach practical, and in 2026 it extended from COVID-19 to influenza.[3][4]

    Editor reviewedStrict sourcingUpdated mRNA and next-gen vaccinesHealth and medicineLife sciences

    The basic idea

    Your cells make proteins by reading short-lived copies of genes called messenger RNA (mRNA). An mRNA vaccine supplies a man-made message that encodes one viral protein. Cells read it, make the protein, and the immune system learns to recognise it.[1] The message is not infectious. It does not enter your genes, and the cell breaks it down through normal processes.[2]

    The COVID-19 vaccines from Pfizer-BioNTech and Moderna both encode the virus’s spike protein.[5]

    Two classes of RNA are studied as vaccines: non-replicating mRNA and self-amplifying RNA derived from viruses.[1] Self-amplifying RNA additionally encodes viral replication machinery (see self-amplifying-rna).[6] The platform is non-infectious and non-integrating, and its RNA is degraded by normal cellular pathways.[2] BNT162b2 and mRNA-1273 encode the full-length SARS-CoV-2 spike and are formulated in lipid nanoparticles.[5]

    What the message looks like

    A vaccine mRNA is built to look like the messages your own cells make. It has the protein recipe in the middle, a protective cap at the front and a tail at the back.[7] The cap is needed for cells to make much protein from it, and the tail helps the message last.[8]

    In vitro transcribed mRNA should contain an open reading frame flanked by 5’ and 3’ UTRs, a 5’ cap and a poly(A) tail, mimicking a mature cytoplasmic mRNA.[7] The cap is required for efficient translation, and the poly(A) tail regulates translation and stability.[8] Removing double-stranded RNA contaminants by chromatography matters too. In one study FPLC purification raised protein output up to 1,000-fold in primary human dendritic cells.[9]

    The problem modified nucleosides solved

    Cells have alarm systems that react to foreign RNA. Small chemical changes to the building blocks of lab-made mRNA, called modified nucleosides, partly quiet this alarm.[10] Katalin Karikó and Drew Weissman shared the 2023 Nobel Prize in Physiology or Medicine for the work.[3]

    Nucleoside modification partially suppresses recognition of double-stranded RNA contaminants and reduces type I interferon signalling.[10] The Nobel committee credited these base-modification discoveries with enabling effective COVID-19 mRNA vaccines.[3]

    Getting the message into cells

    Unprotected mRNA is quickly broken down by enzymes outside cells and is not taken up efficiently.[11] Approved mRNA COVID-19 vaccines package the mRNA in lipid nanoparticles.[5] These particles have four lipid components.[12] Storage is a practical constraint. A 2023 review notes that mRNA vaccines need frozen or ultra-cold storage.[13] The details are covered in how lipid nanoparticles deliver RNA.

    Why speed and manufacturing matter

    Changing an mRNA vaccine mostly means changing its genetic sequence, and the same factory process can make it.[14] CEPI notes that the first mRNA COVID-19 vaccine was authorised in just under a year. Strain-updated versions followed in as little as two to three months.[15]

    mRNA is made by cell-free in vitro transcription, which gives high yields. This supports rapid, inexpensive and scalable manufacturing.[14] CEPI’s 2027-2031 strategy cites mRNA COVID-19 authorisation timelines as evidence that platform technologies can shorten outbreak response.[15]

    Updating for new variants

    Because the antigen is just a sequence, COVID-19 vaccines are re-made each year for the variants in circulation. For 2026-2027 the FDA advised a monovalent vaccine targeting the JN.1-lineage XFG variant, after its advisory committee met in May 2026.[16] It approved updated mRNA vaccines from Pfizer-BioNTech and Moderna on 27 August 2026.[17] Designs also differ. Spikevax encodes the full stabilised spike protein. Moderna’s newer mNEXSPIKE encodes only the spike’s N-terminal and receptor-binding domains, at 10 micrograms per dose.[17][18] In the US these vaccines are approved for people 65 and older and younger people with high-risk conditions.[19]

    Beyond COVID-19

    In August 2026 the FDA approved Moderna’s mFLUSIVA for adults 50 and older, the first mRNA influenza vaccine.[4] Its phase 3 trial enrolled 40,805 adults and compared it with a licensed standard-dose vaccine.[20] It showed about 26.6% relative efficacy against confirmed influenza-like illness.[21] Not every target has worked. Moderna’s norovirus candidate did not meet the criteria for early success at a phase 3 interim analysis.[22] The same platform also underlies personalised cancer vaccines such as intismeran-autogene.[23]

    This page describes how the technology works and its regulatory status. It is not medical advice.

    Questions readers ask

    Why did the Nobel Prize go to mRNA research in 2023?

    Katalin Karikó and Drew Weissman were recognised for discoveries on nucleoside base modifications that enabled effective mRNA vaccines against COVID-19.[3]

    Does vaccine mRNA stay in the body?

    A foundational review describes mRNA as non-integrating and degraded by normal cellular processes.[2]

    How quickly can mRNA vaccines be updated?

    CEPI notes that after the first mRNA COVID-19 vaccine was authorised in just under a year, strain-updated versions were authorised in as little as two to three months.[15]

    How well does the mRNA flu vaccine work compared with a standard flu shot?

    In its phase 3 trial, mFLUSIVA showed about 26.6% relative vaccine efficacy against confirmed influenza-like illness compared with a standard-dose flu vaccine.[21]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      Two major types of RNA are studied as vaccines, non-replicating mRNA and virally derived self-amplifying RNA. confirmedas of 2018-01-12

    2. [2]

      mRNA is a non-infectious, non-integrating platform that is degraded by normal cellular processes. confirmedas of 2018-01-12

    3. [3]

      The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for discoveries on nucleoside base modifications that enabled effective mRNA vaccines against COVID-19. confirmedas of 2023-10-02

    4. [4]

      In August 2026 the FDA approved Moderna's mFLUSIVA (mRNA-1010) for adults 50 and older, the first mRNA-based influenza vaccine and Moderna's fourth FDA-approved product after Spikevax, mRESVIA and mNEXSPIKE. confirmedas of 2026-08-06

    5. [5]

      The first authorized mRNA COVID-19 vaccines, Pfizer-BioNTech's BNT162b2 and Moderna's mRNA-1273, both encode the SARS-CoV-2 spike protein and are formulated in lipid nanoparticles. confirmedas of 2023-03-01

    6. [6]

      Self-amplifying RNA encodes both the antigen and viral replication machinery, which lets the RNA copy itself inside the cell and produce abundant protein. confirmedas of 2018-01-12

    7. [7]

      Lab-made (in vitro transcribed) mRNA is built to resemble a mature cellular mRNA, with an open reading frame for the protein flanked by untranslated regions, a 5' cap and a poly(A) tail. confirmedas of 2018-01-12

    8. [8]

      The 5' cap is required for efficient protein production from mRNA, and the poly(A) tail helps regulate translation and stability. confirmedas of 2018-01-12

    9. [9]

      Double-stranded RNA contaminants can be removed from lab-made mRNA by chromatography, and such purification increased protein production by up to 1,000-fold in primary human dendritic cells in one study. confirmedas of 2018-01-12

    10. [10]

      Chemically modified nucleosides in synthetic mRNA partially suppress recognition of double-stranded RNA and reduce type I interferon signalling, an innate immune alarm response. confirmedas of 2018-01-12

    11. [11]

      Unprotected ("naked") mRNA is quickly degraded by enzymes outside cells and is not taken up efficiently, which is why carriers are needed. confirmedas of 2018-01-12

    12. [12]

      Lipid nanoparticles used for mRNA delivery usually contain four components, an ionizable lipid, a PEG-linked lipid, cholesterol and a phospholipid (helper lipid). confirmedas of 2023-03-01

    13. [13]

      A 2023 review notes that mRNA vaccines need frozen or ultra-cold storage (about -20 to -80 °C), a logistical hurdle for low-resource settings. confirmedas of 2023-03-01

    14. [14]

      mRNA vaccines can potentially be manufactured rapidly, cheaply and at scale, mainly because in vitro transcription reactions give high yields. confirmedas of 2018-01-12

    15. [15]

      CEPI's 2027-2031 strategy notes that the first mRNA COVID-19 vaccine was authorised in just under a year and later strain-updated vaccines in as little as two to three months. confirmedas of 2026-02-01

    16. [16]

      After its vaccine advisory committee met on 28 May 2026, the FDA advised manufacturers that 2026-2027 COVID-19 vaccines for the US should be monovalent vaccines targeting the JN.1-lineage XFG variant. confirmedas of 2026-05-29

    17. [17]

      On 27 August 2026 the FDA approved 2026-2027 formula versions of the mRNA vaccines Comirnaty, Spikevax and mNEXSPIKE, which target the XFG variant; Novavax's protein-based Nuvaxovid was also approved for the season. confirmedas of 2026-08-27

    18. [18]

      mNEXSPIKE encodes only two parts of the coronavirus spike protein, the N-terminal domain and the receptor-binding domain, at a 10-microgram dose in its 2026-2027 formula. confirmedas of 2026-08-28

    19. [19]

      The 2026-2027 approvals kept the narrower US eligibility set in 2025, covering everyone 65 and older plus younger people with at least one high-risk condition, from age 5 for Comirnaty, 6 months for Spikevax and 12 for mNEXSPIKE. confirmedas of 2026-08-28

    20. [20]

      The phase 3 trial behind mFLUSIVA enrolled 40,805 adults aged 50 and older in 11 countries and compared it with a licensed standard-dose flu vaccine. confirmedas of 2026-08-06

    21. [21]

      mFLUSIVA showed about 26.6% relative vaccine efficacy against confirmed influenza-like illness compared with a standard-dose flu vaccine. confirmedas of 2026-08-06

    22. [22]

      Moderna's norovirus vaccine candidate mRNA-1403 did not meet the statistical criteria for early success at a phase 3 interim analysis, the company reported in July 2026. confirmedas of 2026-07-31

    23. [23]

      Each intismeran dose is a synthetic mRNA encoding up to 34 neoantigens chosen from the mutations in that patient's own tumour. confirmedas of 2026-08-19

    Revision history (2)
    1. Page created.
    2. Added how the mRNA molecule is built and purified, and how vaccines are updated for new variants (2026-2027 XFG formula, mNEXSPIKE design).

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "How mRNA vaccines work." ContentLora, updated Oct 10, 2026. https://contentlora.com/explain/how-mrna-vaccines-work

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