In August 2026, the U.S. Food and Drug Administration (FDA) approved Moderna's mFLUSIVA (mRNA-1010), the world's first mRNA-based influenza vaccine, for active immunization in adults aged 50 and older to prevent influenza caused by influenza virus subtypes A and type B represented in the vaccine. [1]

Following the successful deployment of mRNA vaccines against COVID-19, this approval represents the first regulatory authorization of an mRNA vaccine platform for seasonal influenza. It highlights the transition of mRNA technology from an emergency response platform during the pandemic to a broader vaccine development platform capable of supporting routine immunization programs.

The approval followed two regulatory pathways:

• ● For adults aged 50–64 years, mFLUSIVA received full approval based on safety, immunogenicity, and clinical efficacy data;
• ● For adults aged 65 years and older, the vaccine received accelerated approval based on comparative immunogenicity data, as well as supportive evidence, and a postmarketing Phase 4 randomized confirmatory study requirement.

This bifurcated approval reflects mFLUSIVA's current evidence base: while head-to-head trials demonstrated its superiority over standard-dose (SD) conventional flu vaccines, questions remain regarding whether it outperforms high-dose, adjuvanted, or recombinant flu shots in older adults—the population most requiring enhanced protection.

Phase 3 Clinical Trial Data

1. Adults Aged 50–64 (Traditional Approval):

The FDA's approval of mFLUSIVA in adults 50 through 64 years of age was based on a randomized, observer-blind, active-controlled Phase 3 trial enrolling 40,805 adults aged 50 and older across 11 countries. The primary objectives were to evaluate the safety and reactogenicity of mFLUSIVA and to compare its relative vaccine efficacy (rVE) against a standard-dose (SD) active comparator vaccine for preventing influenza-like illness (ILI) caused by any influenza A or B virus strain.

mFLUSIVA met pre-specified superiority criteria, demonstrating an overall rVE of 26.6% (95% CI: 16.7%–35.4%). Strain-specific rVE was: A/H1N1 (29.6%),  A/H3N2 (22.2%), B/Victoria (29.1%).

2. Adults Aged 65 and Older (Accelerated Approval)

The approval in adults 65 years of age and older was based on results from a randomized, observer-blind, active-controlled clinical trial. The study enrolled 2,992 participants aged 65 years and older and primarily evaluated immune responses induced by mFLUSIVA compared with a high-dose inactivated influenza vaccine.

Although mFLUSIVA generated robust immune responses in this population, its clinical benefit in reducing influenza-related disease outcomes among older adults will require confirmation through post-marketing confirmatory clinical studies.

Mechanism and Composition of mFLUSIVA

mFLUSIVA is a trivalent mRNA-lipid nanoparticle (LNP) influenza vaccine that delivers mRNA encoding full-length, membrane-bound influenza hemagglutinin (HA) glycoproteins of the seasonal influenza subtypes A/H1N1 and A/H3N2 and type B/Victoria-lineage.

Following vaccination, LNPs facilitate delivery of mRNA into host cells, where the mRNA serves as a template for antigen production. The expressed viral antigens are subsequently recognized by the immune system, inducing antigen-specific immune responses.

How Do mRNA Vaccines Work?

mRNA vaccines are a class of vaccine that utilize messenger RNA (mRNA) technology to deliver specific pathogen mRNA to the body, prompting the production of corresponding antigen proteins and inducing protective immune responses.

After delivery into cells, typically using lipid nanoparticles (LNPs) or other delivery systems, the mRNA is translated into the target antigen in the cytoplasm. The antigen is then processed and presented through MHC class I and class II pathways, activating cytotoxic T cells (CD8⁺ T cells) and helper T cells (CD4⁺ T cells), respectively. This coordinated process induces a targeted and robust immune response.

Advantages of mRNA Vaccines

Compared with other types of vaccine platforms, mRNA vaccines offer several advantages. [2]

1. Efficient manufacturing and scale-up

mRNA vaccines can be produced using cell-free, enzymatic processes without growing live pathogens or relying on complex cell culture systems, hence allowing rapid, scalable, and cost-effective production.

2. Favorable safety profile

mRNA is non-infectious, acts in the cytoplasm, and does not integrate with the host DNA. It is also naturally degraded after protein expression.

3. Antigen and immune-response optimization

mRNA sequences can be engineered to improve RNA stability, antigen expression, and translational efficiency. Antigen selection and sequence optimization can further enhance the quality and magnitude of the immune response while controlling unwanted innate immune activation.

4. Potential for multivalent and combination vaccines

mRNA vaccines have the exceptional ability to encode multiple antigens, thereby providing a practical approach to developing multivalent vaccines against pathogens with multiple circulating strains and combination vaccines targeting more than one pathogen.

mRNA Vaccines in Infectious Disease And Cancer Therapy

Beyond commercialized COVID-19, respiratory syncytial virus (RSV) and seasonal influenza vaccines, mRNA platforms are advancing rapidly across complex viral pathogens and oncology.

FDA-Approved mRNA Vaccines

As of 2026, five mRNA vaccines have received FDA approval for COVID-19 and RSV, and influenza.

​Table 1. FDA Approved mRNA Vaccines for Infectious Disease

mRNA Vaccines for Infectious Diseases

mRNA-based candidates are also being developed for human immunodeficiency virus (HIV), cytomegalovirus (CMV), and other infectious diseases.

Human Immunodeficiency Virus (HIV)

The versatility of mRNA allows rapid testing and multi-antigen combinations to induce broadly neutralizing antibodies (bNAbs) against highly variable HIV strains. Currently, several clinical trials are underway to assess the effectiveness and safety of mRNA‐based HIV vaccines.

mRNA-1644 (Moderna/NIH): mRNA-1644 is designed to stimulate B cells of the immune system to generate broadly neutralizing antibodies (bnAbs) against the virus (Phase 1).

BNT168 (BioNTech): BNT168 targets a distinct unmet need: enabling HIV-positive individuals to maintain viral suppression without continuous antiretroviral therapy through vaccine-induced cellular immunity. BioNTech has registered a randomized, placebo-controlled Phase I/II clinical trial (NCT07698600) of BNT168. [3]

IAVI G004 (IAVI/Moderna): IAVI G004 is an early‑stage (Phase 1) clinical trial designed to advance the IAVI/Scripps Research strategy for HIV vaccine development. [4]

Cytomegalovirus (CMV)

CMV is a major cause of congenital infection and can lead to serious complications in newborns.

mRNA-1647 (Moderna): mRNA-1647 is an investigational mRNA-based CMV vaccine that encodes glycoprotein B (gB) and pentamer, important antigenic targets of the human immune response to CMV infection. The topline results from a Phase 3 pivotal trial showed thatmRNA-1647 did not meet its primary efficacy endpoint,  leading to its development halt.[5]

Preclinical and early-stage clinical development is ongoing for high-consequence viral threats, including Zika, Ebola, Nipah, and Rabies viruses.

mRNA Vaccines in Cancer Therapy

In clinical practice, mRNA vaccines are classified as either prophylactic or therapeutic: prophylactic vaccines aim to prevent tumor development in high‐risk populations by encoding tumor antigens, while therapeutic vaccines target patients with existing tumors, eliciting immune responses to attack and eliminate cancer cells.

Intismeran autogene (mRNA-4157/V940, Moderna/Merck): Intismeran autogene is a novel, potential first-in-class investigational mRNA-based individualized neoantigen therapy (INT) jointly developed by Merck and Moderna. On August 19, 2026, Moderna and Merck announced positive topline results from the Phase 3 INTerpath-001 trial evaluating adjuvant treatment with intismeran autogene in combination with KEYTRUDA® (pembrolizumab) in patients with completely resected stage IIB-IV melanoma. This represents the first positive Phase 3 readout for an INT and for an mRNA-based cancer therapy, as well as the first and only combination regimen to demonstrate statistically significant and clinically meaningful improvements in RFS and DMFS compared to KEYTRUDA alone for these patients in the adjuvant melanoma setting. [6]

mRNA-4359 (Moderna): mRNA-4359 is an investigational immunotherapy designed to activate antigen-specific T cells that target both PD-L1 and IDO1 expressed by tumor and immunosuppressive cells. Currently in Phase 1/2 clinical testing in combination with pembrolizumab for advanced or metastatic solid tumors and result showed that mRNA-4359 + pembro demonstrated a manageable safety profile in pts with previously untreated locally advanced or metastatic melanoma. [7]

Autogene Cevumeran (BNT122 / RO7198457, BioNTech / Genentech): Autogene Cevumeran is an individualized neoantigen therapy utilizing an un-complexed RNA-lipoplex formulation. Currently in Phase 2 clinical trials for resected pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. [8]

Conclusions and Future Prospects

mRNA technology has expanded rapidly from its initial application in COVID-19 vaccination to a broader platform for infectious disease prevention and cancer immunotherapy. Compared with conventional vaccines, mRNA vaccines offer several advantage.

However, challenges remain, including RNA and formulation stability, delivery efficiency, durability of immune responses, reactogenicity, manufacturing costs, and the need to demonstrate consistent clinical benefit across different diseases. Continued advances in mRNA engineering, lipid nanoparticle delivery, and antigen design will be important for translating the potential of mRNA vaccines into broader clinical applications.
 

Supporting RNA Therapeutics with PEG and Nucleic Acid Building Blocks

The development of RNA-based therapeutics relies on a range of specialized building blocks and delivery materials. Lipids and functional PEG derivatives are widely used in nanoparticle formulations, conjugation strategies, and targeted delivery systems, while phosphoramidites and other nucleic acid building blocks support the synthesis and modification of therapeutic oligonucleotides. Biopharma PEG provides Lipids, PEG derivatives, and PEG-lipid related materials for research and development in RNA therapeutics, including siRNA delivery, conjugation, and lipid nanoparticle (LNP) applications.

We also peovide a range of Nucleic Acid Chemistry products, including RNA Phosphoramidites, LNA & BNA Phosphoramidites, Special & Modified Phosphoramidites, GalNAc Conjugation Building Blocks, Lipid Phosphoramidites, PMO & Morpholino Monomers, Fluorescent & Biotin Labeled Nucleotides, and Nucleic Acid Building Blocks. By supplying reliable, high-purity reagents and advanced delivery materials, Biopharma PEG helps biopharmaceutical researchers streamline the transition from oligonucleotide discovery to advanced clinical platforms.

References:
[1] FDA Approves mFLUSIVA (influenza vaccine, mRNA) for the Prevention of Seasonal Influenza https://www.drugs.com/newdrugs/fda-approves-mflusiva-influenza-vaccine-mrna-prevention-seasonal-influenza-6855.html
[2] Li J, Liu Y, Dai J, Yang L, Xiong F, Xia J, Jin J, Wu Y, Peng X. mRNA Vaccines: Current Applications and Future Directions. MedComm (2020). 2025 Oct 30;6(11):e70434. doi: 10.1002/mco2.70434. PMID: 41179708; PMCID: PMC12572956.
[3] https://allsci.com/news/clinical-trials/first-in-human-trials/biontech-advances-mrna-therapeutic-hiv-vaccine-into-randomized-phase-i-ii-trial/ BioNTech advances mRNA therapeutic HIV vaccine into randomized Phase I/II trial
[4] https://www.iavi.org/press-release/iavi-announces-first-vaccinations-in-iavi-g004-a-phase-1-clinical-trial-of-a-promising-hiv-vaccine-approach/ IAVI announces first vaccinations in IAVI G004, a Phase 1 clinical trial of a promising HIV vaccine approach
[5] https://www.modernatx.com/media-center/all-media/blogs/phase-3-cmv-vaccine-readout-reflections Reflecting on Moderna’s Phase 3 CMV Vaccine Readout
[6] https://www.merck.com/news/merck-and-moderna-announce-phase-3-interpath-001-trial-of-intismeran-autogene-plus-keytruda-met-endpoints-of-recurrence-free-survival-rfs-and-distant-metastasis-free-survival-dmfs-in-patient/  Merck and Moderna Announce Phase 3 INTerpath-001 Trial of Intismeran Autogene Plus KEYTRUDA® Met Endpoints of Recurrence-Free Survival (RFS) and Distant Metastasis-Free Survival (DMFS) in Patients With Completely Resected Stage IIB-IV Melanoma
[7] https://aacrjournals.org/cancerres/article/86/8_Supplement/CT106/782912/Abstract-CT106-First-Line-mRNA-4359-plus Abstract CT106: First-Line mRNA-4359 plus pembrolizumab (pembro) in locally advanced or metastatic melanoma: Results from the phase 1/2 mRNA-4359-P101 study
[8] https://www.gene.com/medical-professionals/pipeline/autogene-cevumeran#autogene-cevumeran-solid-tumors 

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