{"id":"doi:10.1080/22221751.2026.2668752","kind":"article","title":"Enhanced immunogenicity and dose-sparing efficacy of self-amplifying RNA vaccines against seasonal influenza across subtypes","authors":["Huang M","Quan Y","Chen R","Gu H","Song W","Zhu F","Feng S","Lin J","Lu J","Li X","Li W","Pan Q","Li H","Sun L","Jiang T","Zhang B","Yin X","Wei D","Yang C","Liu D","Wang Z","Jia W","Zhao J","Yu J","Yu X"],"author_count":30,"year":2026,"published":"2026-05-19","venue":"Emerging microbes & infections","cited_by":2,"doi":"10.1080/22221751.2026.2668752","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1080/22221751.2026.2668752","archive_url":"https://space-kitty.com/papers/doi:10.1080/22221751.2026.2668752","updated":null,"pmid":"42081324","pmcid":"PMC13188553","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13188553/pdf","abstract":"Recent clinical data on seasonal influenza mRNA vaccines have demonstrated suboptimal efficacy against the influenza B virus (IBV). We employed sequence optimization strategies that successfully enhanced the antigen expression of hemagglutinin (HA) and developed mRNA vaccine candidates targeting the WHO-recommended strains. When administered at a low dose (0.1 μg), both mono-and trivalent influenza A mRNA vaccines induced robust humoral immunity and conferred complete protection against homologous viral challenge in murine models, outperforming the quadrivalent inactivated vaccine (QIV, 2 μg). In contrast, IBV mRNA vaccines at an equivalent dose failed to elicit detectable antibodies and offered no protection, consistent with prior evidence of suboptimal immunogenicity in human trials. These findings highlight strain-specific immunogenicity constraints inherent to conventional mRNA platforms. To overcome these limitations, we systematically compared three distinct RNA vaccine modalities: (1) nucleoside-modified mRNA, (2) self-amplifying RNA (saRNA), and (3) circular RNA (circRNA). Notably, a single 0.1 µg dose of the trivalent saRNA vaccine elicited robust humoral immunity and provided complete protection against IBV challenge, whereas mRNA vaccination achieved only 14% survival. Importantly, long-term antibody monitoring over 20 weeks showed that saRNA at the low 0.1 μg dose maintained high antibody levels, with a markedly more durable response to IBV antigens than those of other platforms. Moreover, the trivalent mRNA vaccine exhibited a favourable safety profile, with no obvious abnormal body weight changes or serum biochemical abnormalities observed after immunization. Our findings advocate for strain-adaptive platform selection: conventional mRNA for generating rapid, high-magnitude responses against influenza A and next-generation saRNA vaccines for enhanced dose efficiency, particularly against IBV.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Enhanced immunogenicity and dose-sparing efficacy of self-amplifying RNA vaccines against seasonal influenza across subtypes\" by Huang M, Quan Y, Chen R et al., https://doi.org/10.1080/22221751.2026.2668752, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}