This article is sponsored by Refeyn.
mRNA vaccines are easily programmable medicines that offer several advantages over traditional vaccines. By providing human cells with the blueprint for key antigen proteins, they can stimulate robust immune responses. While they became widely employed during the COVID-19 pandemic, researchers are now using mRNA vaccines to treat and help prevent a range of other diseases, including viral, parasitic, and bacterial infections, and cancers. In this article, explore how RNA vaccines work, how they were developed, and their advantages, applications, challenges, and emerging areas of research.
RNA Vaccines: The Basics
What is an RNA vaccine?
RNA vaccines, or messenger RNA (mRNA) vaccines, are a relatively new type of vaccine that delivers mRNA molecules to human cells, instructing them to produce specific antigens.1 In the case of viral mRNA vaccines, the mRNA sequence is produced from a DNA template and typically encodes part of a protein found on the viral capsid. The mRNA is then encapsulated in a lipid nanoparticle (LNP). In this application, mRNA vaccines induce an immune response that primes the body to combat a future infection with the real target.
There are two key types of RNA vaccines: Non-replicating synthetic mRNA vaccines and self-amplifying RNA (saRNA) vaccines.2 The former encodes the target antigen and 5’ and 3’ untranslated regions of the mRNA, while the latter also contains extra mRNAs that encode replicase proteins, allowing for intracellular RNA amplification and, therefore, higher antigen production from a lower initial vaccine dose.2
How do RNA vaccines work?
Doctors administer mRNA vaccines via intramuscular injection, which causes local inflammation and recruits immune cells, such as neutrophils, monocytes, and dendritic cells (DCs), to the injection site.3 It is these immune cell subsets that are the primary target for LNP-coated vaccine uptake. DCs are particularly crucial because they are potent antigen-presenting cells; they translate the mRNA template into protein and place it on their surface.4 After traveling to nearby lymph nodes, DCs present this antigen to other immune cells, such as T cells and B cells.3
After recognizing the antigen, helper CD4+ T cells bind to B cells and secrete chemical messengers called cytokines, causing the B cells to proliferate and produce antibodies against the target pathogen.4 DCs and other antigen-presenting cells, such as monocytes and macrophages, also help prime killer CD8+ T cells, which can kill viruses through antibody recognition.3
mRNA vaccines induce an immune response that primes the body to combat specific antigen sources, such as viruses.
modified from © istock.com, Pikovit44, ai_yoshi, Trinset, Olga Dubrovina
mRNA vaccine history and development
Researchers became interested in using mRNA therapeutically in the early 1990s, but for many years, mRNA’s instability and challenges with its delivery prevented any significant progress in vaccine development. For instance, when researchers delivered in vitro transcribed mRNA to DCs, they recognized it as foreign and released inflammatory cytokines.
Finally, in 2005, biochemist Katalin Karikó and her colleagues at the University of Pennsylvania School of Medicine, including immunologist Drew Weissman, published a landmark study. By adding specific chemical modifications commonly found on mammalian mRNA molecules to their in vitro transcribed mRNA, the team was able to avoid inflammatory immune responses and achieve greater target protein translation.5
Combined with advances in LNP technology that facilitated uptake of mRNA by human cells, this breakthrough meant that mRNA vaccines had finally become a viable medicine, but they were not widely used for another 15 years.3 Karikó and Weissman later won the Nobel Prize for Physiology or Medicine in 2023, after their discoveries helped scientists rapidly develop mRNA vaccines for the SARS-CoV-2 virus.
Advantages of RNA vaccines
There are several key advantages of mRNA vaccines compared to other vaccine types. Firstly, mRNA vaccines are highly programmable, allowing researchers to adapt them for any target, from infectious diseases to cancer, without starting from scratch.1 This makes them highly applicable in the context of personalized medicine. They can also be used to target multiple antigens in a single therapy.
Additionally, producing other vaccine types, including live-attenuated, inactivated, toxoid, and recombinant/conjugate vaccines, all require large-scale culture of the live target pathogens to produce the final drug product. This process carries biosecurity risks and is time- and cost-intensive. In contrast, manufacturing mRNA vaccines does not scientists to grow live pathogens. Instead, researchers only need the genome sequencing data from the target pathogen, eliminating risks, accelerating the development process, and lowering costs.
Finally, unlike DNA vaccines, mRNA vaccines carry no risk of integration into the host cell genome and are delivered in an LNP rather than a viral vector, meaning that patients can receive multiple doses without the concern of prior exposure and immunity to the viral vectors.1
Applications of RNA Vaccines
RNA vaccines for infectious disease
The first and best-known examples of approved mRNA vaccines are those developed during the global COVID-19 pandemic to combat SARS-CoV-2 infection. Researchers took advantage of pre-existing mRNA and LNP technologies to rapidly produce multiple mRNA vaccines for the virus, targeting the viral spike protein that allows it to infect human cells.
Researchers are now developing mRNA vaccines for many different infectious diseases. For example, in ongoing clinical trials, scientists are testing mRNA vaccines against multiple strains of influenza, including the H5N1 avian influenza. Scientists are also investigating mRNA vaccines for other viral infections, including human immunodeficiency virus, cytomegalovirus, respiratory syncytial virus, Zika virus, and rabies, as well as parasitic infections such as malaria.6 Recent research has shown that bacterial infections, including tuberculosis, can also be targeted with mRNA vaccines.7
RNA cancer vaccines
mRNA vaccines are also highly applicable in the treatment of cancer. Researchers sequence the genomes of patients’ tumors and design mRNA molecules that encode specific tumor neoantigens to elicit stronger immune responses. Because mRNA vaccines are easily programmable and can be produced rapidly, researchers can create a personalized vaccine for each individual patient. In cases where some cancer cells are resistant to the original vaccine or other treatments, scientists can potentially produce multiple vaccines to target other neoantigens.
For example, in an ongoing Phase 3 clinical trial, researchers are investigating personalized mRNA vaccines to treat non-small-cell lung cancer (NSCLC). After surgical resection, clinicians sequence the genomes of the NSCLC tumors and design individualized mRNA vaccines targeting up to 34 neoantigens.8 Clinicians then administer the vaccines as a combination therapy with the immune checkpoint inhibitor pembrolizumab. Researchers are also exploring this combination therapy approach in other types of cancer, including melanoma, pancreatic cancer, and brain tumors.
In another recent study, researchers found that that injecting mRNA COVID-19 vaccines into tumors could sensitize tumors to immune checkpoint inhibitors and help elicit anti-tumor immune responses.9
Challenges, Advances, and Future Directions
The mRNA vaccine field is developing rapidly, with researchers working to optimize immune responses, improve delivery, and investigate nascent applications. One emerging research area is “naked” mRNA vaccines, which do not use a carrier like an LNP or viral vector.10 This type of mRNA vaccine has several advantages, including accelerated production, less complex manufacturing requirements, and controllable protein expression at the injection site; however, they also have major limitations, such as instability and low cellular uptake.10
Researchers are also exploring the potential to target DCs for better uptake of mRNA vaccines to stimulate more robust immune responses and avoid systemic uptake and off-target effects such as inflammation.4 Other researchers are investigating universal mRNA cancer vaccines that could be used to prompt strong immune responses against multiple unrelated tumors.11
- Li J, et al. mRNA Vaccines: Current applications and future directions. MedComm. 2025;6(11):e70434.
- Pardi N, et al. mRNA vaccines — A new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261-279.
- Verbeke R, et al. Innate immune mechanisms of mRNA vaccines. Immunity. 2022;55(11):1993-2005.
- Clemente B, et al. Straight to the point: Targeted mRNA-delivery to immune cells for improved vaccine design. Front Immunol. 2023;14.
- Karikó K, et al. Suppression of RNA recognition by toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity. 2005;23(2):165-175.
- Sofroniou A, Ridley A. A systematic review of clinical trials using mRNA vaccines for infectious diseases other than COVID-19. Br J Biomed Sci. 2025;82:14557.
- Lukeman H, et al. An LNP-mRNA vaccine modulates innate cell trafficking and promotes polyfunctional Th1 CD4+ T cell responses to enhance BCG-induced protective immunity against Mycobacterium tuberculosis. EBioMedicine. 2025;113:105599.
- Lee, JM, et al. The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non–small-cell lung cancer (NSCLC). J Clin Oncol.2024;42(16):TPS8116.
- Grippin AJ, et al. SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade. Nature. 2025;647(8089):488-497.
- Abbasi S, et al. Carrier-free mRNA vaccine induces robust immunity against SARS-CoV-2 in mice and non-human primates without systemic reactogenicity. Mol Ther. 2024;32(5):1266-1283.
- Qdaisat S, et al. Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading. Nat Biomed Eng. 2025;9(9):1437-1452.
