Et nyt RCT viser at en modRNA influenzavaccine er mere effektiv end den traditionelle influenzavaccine, men også giver flere bivirkninger.
Baggrund
Under COVID-19 viste mRNA vacciner at være effektive, og samtidig hurtige at udvikle og tilpasse til nye varianter. Traditionelle influenzavacciner har ikke været så effektive som mange andre vacciner, og spørgsmålet er så om man kan lave mRNA vacciner der er bedre. Det er der blevet udviklet, og et RCT studie undersøger effektiviteten og sikkerheden ved denne.
ModRNA vacciner anvender nukleosidmodificeret mRNA hvor man udskifter uridin med pseudouridin, hvilket giver et mindre immunrespons mod vaccinerne, og dermed gør dem mere stabile i kroppen og mere effektive sammenlignet med rene mRNA vacciner. COVID-19 vaccinerne kaldes ofte for mRNA vacciner, men var faktisk modRNA vacciner.
Om studiet
I studiet blev 18.476 deltagere randomiseret til enten at modtage den nye modRNA influenzavaccine eller en traditionel inaktiveret vaccine. Man fulgte så deltagerne i 6 måneder efter, og så på antallet af laboratoriebekræftede tilfælde af influenza der kom. Her viste resultatet at dem der fik modRNA vaccinen havde mindre risiko for at få influenza end dem der fik en traditionel vaccine. Der blev set 57 tilfælde i modRNA vaccine gruppen og 87 i kontrolgruppen.
På baggrund af den kendte effektivitet af den traditionelle vaccine (der er 44-54% hos yngre) har man estimeret at modRNA vaccinen vil give en effektivitet på 60-67%.
Det bør dog bemærkes at man i studiet kun inkluderede deltagere i alderen 18-64 år, og derfor ekskluderede ældre fra studiet. Man ved derfor ikke effekten og sikkerheden ved ældre, der har højere risiko ved at få en influenzainfektion.
Man så flere bivirkninger ved modRNA vaccinen. Man så bl.a. lokale reaktioner på 70,1% i dem der fik modRNA vaccinen sammenlignet med 43,1% ved den traditionelle vaccine. Systemiske bivirkinger blev set i hhv. 65,8% og 48,7% tilfælde. Feber blev set i hhv. 5,6% og 1,7% tilfælde.
Efficacy, Immunogenicity, and Safety of Modified mRNA Influenza Vaccine
METHODS: In this phase 3 trial, we randomly assigned healthy adults between the ages of 18 and 64 years to receive either a quadrivalent modRNA influenza vaccine (modRNA group) or a licensed inactivated quadrivalent influenza vaccine (control group) during the 2022-2023 influenza season in the United States, South Africa, and the Philippines. The primary end point was relative efficacy, defined by the reduction in the percentage of participants with laboratory-confirmed influenza associated with influenza-like illness at least 14 days after vaccination with the modRNA vaccine, as compared with the control vaccine, and analyzed for noninferiority and superiority. Immunogenicity was evaluated by means of a hemagglutination inhibition (HAI) assay. We assessed reactogenicity within 7 days after vaccination, adverse events through 1 month, and serious adverse events through 6 months. We assessed vaccine efficacy, immunogenicity, and safety in the modRNA group.
RESULTS: A total of 18,476 participants underwent randomization: 9225 were assigned to receive the modRNA vaccine and 9251 to receive the control vaccine. The relative efficacy of the modRNA vaccine as compared with the control vaccine against influenza-like illness was 34.5% (95% confidence interval [CI], 7.4 to 53.9) on the basis of 57 cases in the modRNA group and 87 cases in the control group, a finding that met the criteria for both noninferiority and superiority. Cases of influenza-like illness were caused by A/H3N2 and A/H1N1 strains but almost no B strains. The noninferiority of the antibody response on HAI assay was shown for influenza A strains but not for B strains. Primarily mild or moderate reactogenicity was observed in both vaccine groups but was reported more frequently in the modRNA group (overall local reactions, 70.1% vs. 43.1%; overall systemic events, 65.8% vs. 48.7%). Fever occurred in 5.6% of the participants in the modRNA group and in 1.7% of those in the control group. Adverse event profiles were similar in the two groups.
CONCLUSIONS: The modRNA vaccine had statistically superior efficacy over the control vaccine, with greater immune responses to A/H3N2 and A/H1N1 strains, but was associated with more reactogenicity events. (Funded by Pfizer; C4781004 ClinicalTrials.gov number, NCT05540522.)See also in NEJM Evidence: Human clinical trial of a nucleoside-modified mRNA influenza vaccine.
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