[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
Viruses. 2020 Jan 3;12(1). pii: E64. doi: 10.3390/v12010064.
A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses.
Wu F1, Zhang S1,2, Zhang Y1,2, Mo R1,3, Yan F1,4,5, Wang H1,6, Wong G7,8, Chi H1,4,5, Wang T1,4,5, Feng N1,4,5, Gao Y1,4,5, Xia X1,4,5, Zhao Y1,4,5, Yang S1,4,5.
Author information: 1 Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China. 2 College of Wildlife Resources, Northeast Forestry University, Harbin 150040, China. 3 Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China. 4 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. 5 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China. 6 College of Veterinary Medicine, Jilin University, Changchun 130062, China. 7 Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai 20031, China. 8 Special Pathogens Program, Public Health Agency of Canada, Winnipeg, MB R3E3R2, Canada.
Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%-90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research.
KEYWORDS: Sudan virus; horse; mice; purified IgG; vaccine; virus-like particle
PMID: 31947873 DOI: 10.3390/v12010064
Keywords: Ebolavirus; Sudan virus; Vaccines; Animal models.