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

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 i...

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Bibliographic Details
Published in:npj vaccines 2024-08, Vol.9 (1), p.138-13, Article 138
Main Authors: Cui, Xiaole, Vervaeke, Pieter, Gao, Ya, Opsomer, Lisa, Sun, Qing, Snoeck, Janne, Devriendt, Bert, Zhong, Zifu, Sanders, Niek N.
Format: Article
Language:English
Subjects:
631/250/2152/1566/1618
631/250/2152/2153/1291
631/250/590/2293
Antibodies
Antigens
Avian flu
Biodistribution
Biomedical and Life Sciences
Biomedicine
Coronaviruses
COVID-19 vaccines
Disease transmission
Epidemics
Immune response
Immunogenicity
Infectious Diseases
Lipids
Lymph nodes
Lymphatic system
Medical Microbiology
mRNA vaccines
Nanoparticles
Pandemics
Peptides
Poultry
Proteins
Public Health
Vaccine
Vaccines
Virology
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Summary: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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-024-00932-x