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Viruses2020; 12(1); 64; 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.

Abstract: 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.
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Publication Date: 2020-01-03 PubMed ID: 31947873PubMed Central: PMC7019897DOI: 10.3390/v12010064Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates a possible vaccine for the Ebola Sudan virus (SUDV) employing a recombinant baculovirus system. The vaccine candidate, encapsulating SUDV matrix structural protein (VP40) and SUDV glycoprotein (GP), demonstrated promising immunogenicity in mice and horses.

Background and Aims

  • Despite being identified in 1976, Ebola virus (SUDV) continues to be one of the most lethal viruses for humans and nonhuman primates, with a fatality rate between 67% to 90%. The lack of licensed drugs and vaccines makes prevention of the virus extremely difficult.
  • The research aimed to create a vaccine candidate for SUDV using recombinant baculoviruses (rBV) expressing the SUDV matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP).

Methodology

  • SUDV virus-like particles (VLPs) were created 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 verified by Immuno-Fluorescence Assay (IFA) and Western blot analysis.
  • The morphology of SUDV VLPs was assessed using electron microscopy.
  • Mice and horses were immunized with SUDV VLPs to evaluate the immunogenicity of the particles.

Results

  • Vaccination with SUDV VLPs in mice resulted in the production of SUDV GP-specific IgG antibodies. These antibodies neutralised the SUDV GP pseudotyped HIV, meaning they successfully prevented the spread of an infection.
  • A week after primary immunization, significant B cell activation was noted in mice vaccinated with VLPs mixed with Montanide ISA 201.
  • The immunization also increased the frequency of cells secreting type 1 and type 2 cytokines, producing an immune response.
  • Immunizing horses showcased similar outputs, with the production of SUDV GP-specific and neutralizing antibodies against the SUDV virus.

Conclusions

  • The research establishes that the SUDV VLPs generated in this study possess strong immunogenic capacity and propose a hopeful direction for the development of a viable SUDV vaccine.
  • Moreover, the immunoglobulins derived from the immunized horses provide a foundation for future research into therapeutic drugs against SUDV.

Cite This Article

APA
Wu F, Zhang S, Zhang Y, Mo R, Yan F, Wang H, Wong G, Chi H, Wang T, Feng N, Gao Y, Xia X, Zhao Y, Yang S. (2020). A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses. Viruses, 12(1), 64. https://doi.org/10.3390/v12010064

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 12
Issue: 1
PII: 64

Researcher Affiliations

Wu, Fangfang
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
Zhang, Shengnan
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • College of Wildlife Resources, Northeast Forestry University, Harbin 150040, China.
Zhang, Ying
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • College of Wildlife Resources, Northeast Forestry University, Harbin 150040, China.
Mo, Ruo
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.
Yan, Feihu
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.
Wang, Hualei
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • College of Veterinary Medicine, Jilin University, Changchun 130062, China.
Wong, Gary
  • Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai 20031, China.
  • Special Pathogens Program, Public Health Agency of Canada, Winnipeg, MB R3E3R2, Canada.
Chi, Hang
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.
Wang, Tiecheng
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.
Feng, Na
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.
Gao, Yuwei
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.
Xia, Xianzhu
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.
Zhao, Yongkun
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.
Yang, Songtao
  • Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
  • Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China.
  • Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.

MeSH Terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • B-Lymphocytes / immunology
  • Baculoviridae / genetics
  • Baculoviridae / metabolism
  • Cell Line
  • Cytokines / immunology
  • Ebola Vaccines / administration & dosage
  • Ebolavirus / immunology
  • Female
  • Hemorrhagic Fever, Ebola / immunology
  • Hemorrhagic Fever, Ebola / prevention & control
  • Horses
  • Humans
  • Immunization
  • Immunoglobulin G / blood
  • Mice
  • Mice, Inbred BALB C
  • Sf9 Cells
  • Vaccines, Virus-Like Particle / administration & dosage
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology
  • Viral Matrix Proteins / metabolism

Grant Funding

  • 2017YFD0501804 / National Project for Prevention and Control of Transboundary Animal Diseases

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 6 times.
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