Immunogenicity and biodistribution of lipid nanoparticle formulated self-amplifying mRNA vaccines against H5 avian influenza.

Autor: Cui X; Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium., Vervaeke P; Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium., Gao Y; Department of Translational Physiology, Infectiology and Public Health, Ghent University, B-9820, Merelbeke, Belgium., Opsomer L; Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium., Sun Q; Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium., Snoeck J; Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium., Devriendt B; Department of Translational Physiology, Infectiology and Public Health, Ghent University, B-9820, Merelbeke, Belgium., Zhong Z; Department of Pharmaceutics, Ghent University, Ghent, Belgium. zifu.zhong@ugent.be.; Cancer Research Institute (CRIG), Ghent University, 9000, Ghent, Belgium. zifu.zhong@ugent.be., Sanders NN; Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium. niek.sanders@ugent.be.; Cancer Research Institute (CRIG), Ghent University, 9000, Ghent, Belgium. niek.sanders@ugent.be.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2024 Aug 03; Vol. 9 (1), pp. 138. Date of Electronic Publication: 2024 Aug 03.
DOI: 10.1038/s41541-024-00932-x
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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