Filovirus-Like Particles Produced in Insect Cells: Immunogenicity and Protection in Rodents

Background. Virus-like particles (VLPs) of Ebola virus (EBOV) and Marburg virus (MARV) produced in human 293T embryonic kidney cells have been shown to be effective vaccines against filoviral infection. In this study, we explored alternative strategies for production of filovirus-like particle-based...

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Bibliographic Details
Published in:The Journal of infectious diseases 2007-11, Vol.196 (Supplement-2), p.S421-S429
Main Authors: Warfield, Kelly L., Posten, Nichole A., Swenson, Dana L., Olinger, Gene G., Esposito, Dominic, Gillette, William K., Hopkins, Ralph F., Costantino, Julie, Panchal, Rekha G., Hartley, James L., Aman, M. Javad, Bavari, Sina
Format: Article
Language:English
Subjects:
Animals
Baculoviridae
Baculovirus
Cell Line
Dendritic Cells - immunology
Disease Models, Animal
Ebola virus
Ebolavirus - immunology
Ebolavirus - physiology
Female
Filoviridae - immunology
Filoviridae Infections - immunology
Hemorrhagic Fever, Ebola - immunology
Humans
Insect genetics
Insect vectors
Insect viruses
Kidney cells
Marburg virus
Marburg Virus Disease - immunology
Marburgvirus - immunology
Marburgvirus - physiology
Mice
Mice, Inbred C57BL
Prophylaxis and Therapy
Rodentia
T lymphocytes
Vaccination
Virus Replication
Viruses
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Summary:Background. Virus-like particles (VLPs) of Ebola virus (EBOV) and Marburg virus (MARV) produced in human 293T embryonic kidney cells have been shown to be effective vaccines against filoviral infection. In this study, we explored alternative strategies for production of filovirus-like particle-based vaccines, to accelerate the development process. The goal of this work was to increase the yield of VLPs, while retaining their immunogenic properties. Methods. Ebola and Marburg VLPs (eVLPs and mVLPs, respectively) were generated by use of recombinant baculovirus constructs expressing glycoprotein, VP40 matrix protein, and nucleoprotein from coinfected insect cells. The baculovirus-derived eVLPs and mVLPs were characterized biochemically, and then the immune responses produced by the eVLPs in insect cells were studied further. Results. The baculovirus-derived eVLPs elicited maturation of human myeloid dendritic cells (DCs), indicating their immunogenic properties. Mice vaccinated with insect cell—derived eVLPs generated antibody and cellular responses equivalent to those vaccinated with mammalian 293T cell—derived eVLPs and were protected from EBOV challenge in a dose-dependent manner. Conclusion. Together, these data suggest that filovirus-like particles produced by baculovirus expression systems, which are amenable to large-scale production, are highly immunogenic and are suitable as safe and effective vaccines for the prevention of filoviral infection.
ISSN:0022-1899
1537-6613
DOI:10.1086/520612