Novel mRNA Vaccine to Prevent Seasonal Influenza
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on December 12th, 2025
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There are currently two types of vaccines used to prevent influenza: the injectable inactivated influenza vaccine and the live attenuated influenza vaccine. Drawing on experience gained from developing the COVID-19 mRNA vaccines, Pfizer has applied mRNA vaccine technology to create a new influenza vaccine. A study evaluating its safety and effectiveness was recently published in the New England Journal of Medicine.
The trial was conducted in the United States, South Africa, and the Philippines during the 2022–2023 influenza season. A total of 18,476 participants were randomly assigned to receive an intramuscular injection of either the novel mRNA vaccine or a comparator inactivated influenza vaccine. The mRNA vaccine contains 30 micrograms of mRNA encoding the hemagglutinin proteins of the four influenza strains circulating during that season.
The inactivated influenza vaccine contains the same four strains, but the viruses have been chemically inactivated. Because the virus cannot replicate, the resulting immune response may be less robust and may not generate strong immunological memory. An alternative is the live attenuated influenza vaccine, which uses weakened but replication-competent virus. While it elicits a stronger immune response, it requires more stringent storage conditions and carries a small risk of mutation. The mRNA influenza vaccine avoids these challenges because it does not contain viable viruses, yet it can stimulate a stronger immune response than inactivated vaccines by allowing continuous production of viral antigens inside the body.
After 130 days of follow-up, the mRNA influenza vaccine was found to be 34.5 percent more effective than the inactivated comparator in preventing laboratory-confirmed influenza illness. Immunologic analyses also showed that recipients of the mRNA vaccine produced higher levels of antibodies and greater interferon-gamma responses from antigen-specific T lymphocytes, suggesting a more robust cellular and humoral immune response. The researchers noted that future studies are needed to assess the usage of this mRNA influenza vaccine technology across different seasons.
The trial was conducted in the United States, South Africa, and the Philippines during the 2022–2023 influenza season. A total of 18,476 participants were randomly assigned to receive an intramuscular injection of either the novel mRNA vaccine or a comparator inactivated influenza vaccine. The mRNA vaccine contains 30 micrograms of mRNA encoding the hemagglutinin proteins of the four influenza strains circulating during that season.
The inactivated influenza vaccine contains the same four strains, but the viruses have been chemically inactivated. Because the virus cannot replicate, the resulting immune response may be less robust and may not generate strong immunological memory. An alternative is the live attenuated influenza vaccine, which uses weakened but replication-competent virus. While it elicits a stronger immune response, it requires more stringent storage conditions and carries a small risk of mutation. The mRNA influenza vaccine avoids these challenges because it does not contain viable viruses, yet it can stimulate a stronger immune response than inactivated vaccines by allowing continuous production of viral antigens inside the body.
After 130 days of follow-up, the mRNA influenza vaccine was found to be 34.5 percent more effective than the inactivated comparator in preventing laboratory-confirmed influenza illness. Immunologic analyses also showed that recipients of the mRNA vaccine produced higher levels of antibodies and greater interferon-gamma responses from antigen-specific T lymphocytes, suggesting a more robust cellular and humoral immune response. The researchers noted that future studies are needed to assess the usage of this mRNA influenza vaccine technology across different seasons.