Immunogenicity and biodistribution of lipid nanoparticle formulated self-amplifying mRNA vaccines against H5 avian influenza
Open accessAbstract
This study reports on the immunogenicity and biodistribution of H5 hemagglutinin (HA)-based self-amplifying (sa) mRNA vaccines in mice. Four sa-mRNA vaccines encoding either a secreted full-length HA, a secreted HA head domain, a secreted HA stalk domain, or a full-length membrane-anchored HA were investigated. All vaccines elicited an adaptive immune response. However, the full-length HA sa-RNA vaccines demonstrated superior performance compared to head and stalk domain vaccines. The antibody titers positively correlated with the vaccine dose. Cellular immune responses and antigen-specific IgA antibodies in the lungs were also observed. The comparison of the sa-mRNA vaccines encoding the secreted and membrane-anchored full-length HA revealed that anchoring of the HA to the membrane significantly enhanced the antibody and cellular responses. In addition to the injection site, the intramuscularly injected sa-mRNA-LNPs were also detected in the draining lymph nodes, spleen, and to a lesser extent, in the lung, kidney, liver, and heart.
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A lipid nanoparticle (LNP) delivered replicating RNA expressing the HA of clade 2.3.4A/Anhui/1/2005 H5N1 reported low homologous neutralizing activity after a single immunization that was increased after boosting.
“A recent report evaluating the immunogenicity in mice of a lipid nanoparticle (LNP) delivered replicating RNA expressing the HA of clade 2.3.4A/Anhui/1/2005 H5N1 reported low homologous neutralizing activity after a single immunization that was increased after boosting32.”
From Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice (2025) · cites this paper as [32]
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Hawman, D. W., Tipih, T., Hodge, E., Stone, E. T., Warner, N., McCarthy, N., Granger, B., Meade-White, K., Leventhal, S., Hatzakis, K., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55546-7 · Cited by 20 · see citing works
- Authors
- Cui, X., Vervaeke, P., Gao, Y., Opsomer, L., Sun, Q., Snoeck, J., Devriendt, B., Zhong, Z., & Sanders, N. N.
- Affiliations
- Ghent University (BE)
- Corresponding author
- Zhong, Zifu
- Sanders, Niek N.
- ORCID
- Venue
- npj Vaccines
- Published
- 2024-08-03
- Volume
- 9
- Issue
- 1
- Pages
- 138-138
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC11298010
- OpenAlex
- W4401284912
- Cited by
- 33
- References
- 54
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 4
- FWCI
- 10.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Bijzonder Onderzoeksfonds (BOF.BAS.2018.0028.01)
- China Scholarship Council (202107650043)
- Fonds Wetenschappelijk Onderzoek (1172121N, 12K0323N)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- self-amplifying mRNA vaccine, lipid nanoparticles, H5 avian influenza, hemagglutinin, immunogenicity, tissue distribution, antibody response, IgA antibodies, cell-mediated immunity, vaccine dose, intramuscular injection, draining lymph nodes
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