Work

A capless hairpin-protected mRNA vaccine encoding the full-length Influenza A hemagglutinin protects mice against a lethal Influenza A infection

Year: 2025

Type: article

Abstract: The success of mRNA vaccines in controlling the COVID 19 pandemic has confirmed the efficacy of synthetically synthesized mRNA in humans and has also provided a blueprint on how to design them in terms of molecular structure and cost. We describe a mRNA vector that, unlike linear mRNAs used in current vaccines/therapeutics, does not require a 5' cap to function. The described mRNA vector initiates translation from an internal ribosomal entry site (IRES) and contains specially designed self-folding secondary structures (hairpins) to protect the 5' end against degradation, dramatically improving its stability. The produced mRNA did not require any additional modifications for functionality. The 5' hairpins completely inhibited cap-dependent translation, and all vectors containing them required an IRES to express protein. When this capless mRNA vector was constructed to express the full-length Influenza A membrane protein hemagglutinin (HA), complexed with pre-formed lipid-based nanoparticles, and then injected into mice as a vaccine, it generated high titers of anti-HA antibodies and protected mice against a lethal dose of Influenza A.

Source: Gene Therapy

DOI: 10.1038/s41434-025-00521-0

Authors: Victor Solodushko, Jin H. Kim, Brian Fouty

Institutions: University of South Alabama, University of South Alabama Medical Center

Language: English

Topic: Influenza Virus Research Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,790