Navigating the Transition to RNA-Based Influenza Vaccines: A State-of-the-Art Review.
- 1Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 115 27 Athens, Greece.
- 2First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, 106 76 Athens, Greece.
- 32nd Department of Medicine and Laboratory, School of Medicine, National and Kapodistrian University of Athens, General Hospital of Athens "Hippokration", 115 27 Athens, Greece.
Abstract
Seasonal influenza and the ongoing emergence of zoonotic influenza viruses, including highly pathogenic avian influenza A (H5N1), remain substantial global public health threats, underscoring the need for rapidly adaptable vaccine platforms. This state-of-the-art review critically evaluates the clinical development of RNA-based influenza vaccines through a comprehensive assessment of ClinicalTrials.gov records and peer-reviewed literature. Candidates were examined across four domains: seasonal influenza vaccines, pre-pandemic influenza vaccines, combination respiratory vaccines, and self-amplifying RNA (saRNA) platforms. Clinical evidence indicates that mRNA influenza vaccines consistently elicit robust humoral immune responses and, in late-stage trials, have demonstrated improved relative efficacy against influenza A compared with conventional influenza vaccines. Reactogenicity is generally more frequent with mRNA vaccines, particularly with respect to transient mild-to-moderate systemic adverse events. However, serious adverse events remain uncommon and broadly comparable to those observed with licensed comparator vaccines. Pre-pandemic and multicomponent mRNA vaccine candidates similarly demonstrate strong immunogenicity, supporting the potential of RNA platforms for both seasonal vaccination and pandemic preparedness. Clinical development of saRNA influenza vaccines has progressed through early-phase trials, although publicly available clinical data remain limited. Regulatory milestones in 2026, including U.S. approval of mRNA-1010 (mFlusiva), the first approved mRNA-based seasonal influenza vaccine, and European Union authorization of mRNA-1083 (mCOMBRIAX), an mRNA-based influenza-COVID-19 combination vaccine, represent important steps in the clinical transition and implementation of RNA-based influenza vaccination.
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BibTeX
@article{panagiotopoulos2026navigating,
title = {{Navigating the Transition to RNA-Based Influenza Vaccines: A State-of-the-Art Review.}},
author = {Antonios-Periklis Panagiotopoulos and Deny Tsakri and Alexandros Laskaris and Chrysa Saldari and Kyriaki Ranellou and Ilias Mariolis and Athanasios Tsakris and Cleo Anastassopoulou},
journal = {Vaccines},
year = {2026},
month = oct,
doi = {10.3390/vaccines14100874},
url = {https://europepmc.org/article/MED/42931403},
note = {CC BY},
}
RIS
TY - JOUR
TI - Navigating the Transition to RNA-Based Influenza Vaccines: A State-of-the-Art Review.
AU - Antonios-Periklis Panagiotopoulos
AU - Deny Tsakri
AU - Alexandros Laskaris
AU - Chrysa Saldari
AU - Kyriaki Ranellou
AU - Ilias Mariolis
AU - Athanasios Tsakris
AU - Cleo Anastassopoulou
PY - 2026
DA - 2026/10/02
JO - Vaccines
DO - 10.3390/vaccines14100874
UR - https://europepmc.org/article/MED/42931403
AB - Seasonal influenza and the ongoing emergence of zoonotic influenza viruses, including highly pathogenic avian influenza A (H5N1), remain substantial global public health threats, underscoring the need for rapidly adaptable vaccine platforms. This state-of-the-art review critically evaluates the clinical development of RNA-based influenza vaccines through a comprehensive assessment of ClinicalTrials.gov records and peer-reviewed literature. Candidates were examined across four domains: seasonal influenza vaccines, pre-pandemic influenza vaccines, combination respiratory vaccines, and self-amplifying RNA (saRNA) platforms. Clinical evidence indicates that mRNA influenza vaccines consistently elicit robust humoral immune responses and, in late-stage trials, have demonstrated improved relative efficacy against influenza A compared with conventional influenza vaccines. Reactogenicity is generally more frequent with mRNA vaccines, particularly with respect to transient mild-to-moderate systemic adverse events. However, serious adverse events remain uncommon and broadly comparable to those observed with licensed comparator vaccines. Pre-pandemic and multicomponent mRNA vaccine candidates similarly demonstrate strong immunogenicity, supporting the potential of RNA platforms for both seasonal vaccination and pandemic preparedness. Clinical development of saRNA influenza vaccines has progressed through early-phase trials, although publicly available clinical data remain limited. Regulatory milestones in 2026, including U.S. approval of mRNA-1010 (mFlusiva), the first approved mRNA-based seasonal influenza vaccine, and European Union authorization of mRNA-1083 (mCOMBRIAX), an mRNA-based influenza-COVID-19 combination vaccine, represent important steps in the clinical transition and implementation of RNA-based influenza vaccination.
SN - 2076-393X
ER -