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 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.


CONCLUSIONS
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.
Warfield
Kelly L
KL
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
Posten
Nichole A
NA
Swenson
Dana L
DL
Olinger
Gene G
GG
Esposito
Dominic
D
Gillette
William K
WK
Hopkins
Ralph F
RF
Costantino
Julie
J
Panchal
Rekha G
RG
Hartley
James L
JL
Aman
M Javad
MJ
Bavari
Sina
S
D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology / Q000502:physiology; D005260:Female; D016563:Filoviridae / Q000276:immunology; D018702:Filoviridae Infections / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology*; D006801:Humans; D008379:Marburg Virus Disease / Q000276:immunology*; D029024:Marburgvirus / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012377:Rodentia; D014779:Virus Replication