mRNA Vaccine Technology Beyond COVID: Breakthroughs in
Quick Facts
What mRNA Vaccines Are in Development?
Cancer Vaccines
Moderna's mRNA-4157 (V940) showed a 44% reduction in melanoma recurrence when combined with pembrolizumab in the KEYNOTE-942 trial. The vaccine is custom-made per patient in approximately 4–8 weeks. Phase 3 trials are underway for melanoma and other solid tumors including NSCLC.
Combo Respiratory
Moderna and Pfizer are developing combined annual shots targeting COVID and flu, with some candidates also including RSV. Phase 3 results are expected in 2026.
Other
- HIV: Multiple mRNA candidates in early-stage trials, including approaches targeting broadly neutralizing antibodies
- Malaria: BioNTech and others are developing mRNA malaria vaccine candidates, currently in early clinical testing
- Autoimmune: Tolerogenic mRNA approaches are being explored for type 1 diabetes and multiple sclerosis in preclinical and early clinical stages
How Do Personalized Cancer Vaccines Work?
- Tumor sequencing: Identify unique mutations (neoantigens) in the patient's tumor
- AI neoantigen selection: Algorithms select up to 34 of the most immunogenic targets
- mRNA synthesis: A custom mRNA molecule encoding those neoantigens is manufactured
- Nanoparticle delivery: The mRNA is packaged in lipid nanoparticles for efficient immune cell uptake
- Administration: Multiple doses given alongside checkpoint inhibitors such as pembrolizumab
Moderna's mRNA-4157 combined with Keytruda (pembrolizumab) reduced melanoma recurrence by 44% compared to Keytruda alone. Common side effects included injection site reactions and fatigue.
What Are the Challenges?
- Stability: Most mRNA vaccines require refrigeration or freezing. Thermostable formulations are in development.
- Reactogenicity: The strong immune response can cause side effects such as fever, fatigue, and injection site pain. Next-generation lipid nanoparticles aim to reduce reactogenicity.
- Cost: Personalized cancer vaccines are expected to be expensive due to individualized manufacturing, though costs should decrease with scale.
- Durability: Some mRNA vaccines may require booster doses to maintain immunity.
- Targeting: Delivering mRNA to specific organs beyond the liver remains a significant technical challenge.
Frequently Asked Questions
They train the immune system to recognize and attack specific cancer cells based on the patient's unique tumor mutations, unlike chemotherapy which damages all rapidly dividing cells.
A personalized melanoma vaccine could potentially receive approval as early as 2026–2027, pending Phase 3 results. Other cancer types may follow in subsequent years.
Phase 3 trials are in progress. If successful, a combined vaccine could be available for the 2026–2027 respiratory season.
Several mRNA HIV vaccine candidates are in early-stage clinical trials. While promising, they are far from a cure and could potentially become part of a broader prevention or functional cure strategy.
Multiple years of safety data from billions of COVID-19 mRNA vaccine doses have not revealed long-term safety concerns. mRNA is degraded by the body within days and does not alter DNA.
References
- Sahin U, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547(7662):222-226.
- Moderna/Merck. mRNA-4157 (V940) Phase 2b results (KEYNOTE-942). Presented at AACR Annual Meeting 2023; updated data 2024.
- Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261-279.
- Chaudhary N, Weissman D, Whitehead KA. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat Rev Drug Discov. 2021;20(11):817-838.
- Barbier AJ, Jiang AY, et al. The clinical progress of mRNA vaccines and immunotherapies. Nat Biotechnol. 2022;40(6):840-854.