mRNA Vaccines Encoding the HA Protein of Influenza A H1N1 Virus Delivered by Cationic Lipid Nanoparticles Induce Protective Immune Responses in Mice
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The design of the mRNA vaccine involves the selection of in vitro transcription (IVT) systems and nonviral delivery vectors. This study aimed to verify the effect of 5’ and 3’ untranslated region (UTR) sequences on the translation efficiency of mRNA. Three modes of IVT-mRNA systems (IVT-mRNA-n1/n2/n3) with diverse UTRs were constructed, and EGFP (enhanced green fluorescent protein) and HA (hemagglutinin) gene of H3N2 influenza virus were introduced into each of them. The results showed that the mode of 5’ and 3’ UTRs originating from human β-globulin was better than the mode of UTRs from human α-globulin, and the n3 mode was the best. mEGFP-n3, mH3HA-n3, and mLuciferease-n3 were prepared to compare the effect of cationic lipid nanoparticle (LNP) with that of mannose-conjugated LNP (LNP-Man) on the efficiency of gene delivery. The results showed that the effect of LNP-Man was better than that of LNP both in vitro and in vivo. Choosing appropriate ligands might help in vaccine design. After selecting the IVT-mRNA-n3 system and delivery vectors, mRNA vaccines were constructed against the H1N1 influenza virus, and C57BL/6 mice were immunized through intranasal administration. The results showed that mRNA vaccines could elicit both humoral and cellular immune responses and completely protect mice from the tenfold LD50 H1N1 influenza virus challenge.
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Lipid nanoparticle-mRNA vaccines are being investigated as influenza vaccines, with some formulations in clinical trials.
“Lipid nanoparticle–mRNA vaccines are also being investigated as influenza vaccines29,41,156,157,159,184,189–191, with some formulations in clinical trials (Table 1).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [159]
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- Authors
- Zhuang, X., Qi, Y., Wang, M., Yu, N., Nan, F., Zhang, H., Tian, M., Li, C., Lu, H., & Jin, N.
- Affiliations
- Academy of Military Medical Sciences (CN)
- Chinese Academy of Sciences (CN)
- Wenzhou University (CN)
- Yanbian University (CN)
- Jilin University (CN)
- Corresponding author
- Jin, Ningyi
- Venue
- Vaccines
- Publisher
- MDPI AG
- Published
- 2020-03-10
- Volume
- 8
- Issue
- 1
- Pages
- 123
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC7157730
- OpenAlex
- W3011203304
- Cited by
- 132
- References
- 28
- Citations by year
- 2026: 4 · 2025: 27 · 2024: 26 · 2023: 23 · 2022: 29 · 2021: 18 · 2020: 5
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science and Technology Major Project of the Ministry of Science and Technology of China (2018ZX10102-001)
- Changchun Science and technology plan project (19SS016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mRNA vaccines, influenza A (H1N1) virus, hemagglutinin, cationic lipid nanoparticles, 5' and 3' untranslated regions, in vitro transcription, gene delivery, intranasal immunization, humoral immune response, cell-mediated immunity, protective immunity
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