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

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

  • NPJ Vaccines. 2024 Aug 3;9(1):138. doi: 10.1038/s41541-024-00932-x.
Xiaole Cui 1,  Pieter Vervaeke 1,  Ya Gao 2,  Lisa Opsomer 1,  Qing Sun 1,  Janne Snoeck 1,  Bert Devriendt 2,  Zifu Zhong 3 4,  Niek N Sanders 5 6
Affiliations

Affiliations

  • 1 Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium.
  • 2 Department of Translational Physiology, Infectiology and Public Health, Ghent University, B-9820, Merelbeke, Belgium.
  • 3 Department of Pharmaceutics, Ghent University, Ghent, Belgium. zifu.zhong@ugent.be.
  • 4 Cancer Research Institute (CRIG), Ghent University, 9000, Ghent, Belgium. zifu.zhong@ugent.be.
  • 5 Laboratory of Gene Therapy, Faculty of Veterinary Medicine, Ghent University, B-9820, Merelbeke, Belgium. niek.sanders@ugent.be.
  • 6 Cancer Research Institute (CRIG), Ghent University, 9000, Ghent, Belgium. niek.sanders@ugent.be.
PMID: 39097672 DOI: 10.1038/s41541-024-00932-x
Abstract

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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