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An mRNA-LNP-based Lassa virus vaccine induces protective immunity in mice
Mei Hashizume1, Ayako Takashima1, Masaharu Iwasaki1,2,3,4
1Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Journal of Virology
|May 20, 2024
Summary
Novel mRNA vaccines targeting Lassa virus (LASV) components show promise in protecting mice against lethal infection. These LASV vaccines, utilizing surrogate models, bypass the need for high biosafety levels, accelerating development.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Lassa virus (LASV) causes severe hemorrhagic fever, with no approved vaccines available.
- Research is hindered by the need for high biosafety level 4 facilities for live LASV handling.
- Development of effective LASV countermeasures is urgently needed due to widespread infections in West Africa.
Purpose of the Study:
- To evaluate the efficacy of mRNA-lipid nanoparticle (mRNA-LNP) vaccines expressing LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) using surrogate models.
- To assess the protective immune responses induced by these mRNA-LNP vaccines in mouse models.
- To establish a foundation for developing mRNA-LNP-based LASV vaccines that can be studied at reduced biocontainment levels.
Main Methods:
- Mice were immunized with two doses of mRNA-LNP vaccines encoding LASgpc or LCMnp from lymphocytic choriomeningitis virus (LCMV).
- Vaccine efficacy was tested against lethal challenges using recombinant LCMV expressing LASV antigens in various mouse strains (C57BL/6, CBA, FVB).
- Humoral (antibody) and cellular (CD8+ T cell) immune responses were analyzed post-vaccination and challenge.
Main Results:
- mRNA-LNP vaccines conferred protection against lethal recombinant LCMV challenge in multiple mouse models.
- Immunization significantly reduced viral loads and abrogated lethality in challenged mice.
- Robust LASgpc- and LCMnp-specific CD8+ T cell responses were induced, while neutralizing antibodies were not detected.
Conclusions:
- mRNA-LNP vaccines expressing LASV antigens provide protection in surrogate mouse models of Lassa fever.
- These findings support the development of mRNA-LNP-based LASV vaccines using reduced biocontainment.
- The study highlights the potential of CD8+ T cell responses in LASV vaccine efficacy.
