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.
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 humanmyeloid 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.
Authors: Nicholas J Lennemann; Andrew S Herbert; Rachel Brouillette; Bethany Rhein; Russell A Bakken; Katherine J Perschbacher; Ashley L Cooney; Catherine L Miller-Hunt; Patrick Ten Eyck; Julia Biggins; Gene Olinger; John M Dye; Wendy Maury Journal: J Virol Date: 2017-08-10 Impact factor: 5.103
Authors: Mable Chan; Frederick W Holtsberg; Hong Vu; Katie A Howell; Anders Leung; Evelyn Van der Hart; Paul H Walz; M Javad Aman; Shantha Kodihalli; Darwyn Kobasa Journal: J Infect Dis Date: 2018-11-22 Impact factor: 5.226
Authors: Rebecca J Grant-Klein; Louis A Altamura; Catherine V Badger; Callie E Bounds; Nicole M Van Deusen; Steven A Kwilas; Hong A Vu; Kelly L Warfield; Jay W Hooper; Drew Hannaman; Lesley C Dupuy; Connie S Schmaljohn Journal: Hum Vaccin Immunother Date: 2015 Impact factor: 3.452
Authors: M L Boisen; J N Hartnett; A Goba; M A Vandi; D S Grant; J S Schieffelin; R F Garry; L M Branco Journal: Annu Rev Virol Date: 2016-08-15 Impact factor: 10.431
Authors: Yuliang Sun; Ricardo Carrion; Ling Ye; Zhiyuan Wen; Young-Tae Ro; Kathleen Brasky; Anysha E Ticer; E Ellen Schwegler; Jean L Patterson; Richard W Compans; Chinglai Yang Journal: Virology Date: 2008-11-04 Impact factor: 3.616
Authors: S E Goñi; C S Borio; F B Romano; R P Rota; M G Pilloff; J A Iserte; M A Tortorici; B I Stephan; M F Bilen; P D Ghiringhelli; M E Lozano Journal: J Biomed Biotechnol Date: 2010-06-29