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.
Publication Date: 2020-01-03 PubMed ID: 31947873PubMed Central: PMC7019897DOI: 10.3390/v12010064Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
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
Researcher Affiliations
- Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
- Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
- College of Wildlife Resources, Northeast Forestry University, Harbin 150040, China.
- Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
- College of Wildlife Resources, Northeast Forestry University, Harbin 150040, China.
- Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
- Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China.
- 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.
- Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun 130122, China.
- College of Veterinary Medicine, Jilin University, Changchun 130062, China.
- Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai 20031, China.
- Special Pathogens Program, Public Health Agency of Canada, Winnipeg, MB R3E3R2, Canada.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
References
This article includes 39 references
- Baseler L, Chertow DS, Johnson KM, Feldmann H, Morens DM. The Pathogenesis of Ebola Virus Disease.. Annu Rev Pathol 2017 Jan 24;12:387-418.
- . Ebola haemorrhagic fever in Zaire, 1976.. Bull World Health Organ 1978;56(2):271-93.
- . Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team.. Bull World Health Organ 1978;56(2):247-70.
- Adams MJ, Lefkowitz EJ, King AMQ, Harrach B, Harrison RL, Knowles NJ, Kropinski AM, Krupovic M, Kuhn JH, Mushegian AR, Nibert M, Sabanadzovic S, Sanfaçon H, Siddell SG, Simmonds P, Varsani A, Zerbini FM, Gorbalenya AE, Davison AJ. Changes to taxonomy and the International Code of Virus Classification and Nomenclature ratified by the International Committee on Taxonomy of Viruses (2017).. Arch Virol 2017 Aug;162(8):2505-2538.
- Pourrut X, Kumulungui B, Wittmann T, Moussavou G, Délicat A, Yaba P, Nkoghe D, Gonzalez JP, Leroy EM. The natural history of Ebola virus in Africa.. Microbes Infect 2005 Jun;7(7-8):1005-14.
- Bukreyev AA, Chandran K, Dolnik O, Dye JM, Ebihara H, Leroy EM, Mühlberger E, Netesov SV, Patterson JL, Paweska JT, Saphire EO, Smither SJ, Takada A, Towner JS, Volchkov VE, Warren TK, Kuhn JH. Discussions and decisions of the 2012–2014 International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group, January 2012–June 2013.. Arch Virol 2014 Apr;159(4):821-30.
- Coltart CE, Lindsey B, Ghinai I, Johnson AM, Heymann DL. The Ebola outbreak, 2013-2016: old lessons for new epidemics.. Philos Trans R Soc Lond B Biol Sci 2017 May 26;372(1721).
- Leroy E, Baize S, Gonzalez JP. [Ebola and Marburg hemorrhagic fever viruses: update on filoviruses].. Med Trop (Mars) 2011 Apr;71(2):111-21.
- Ascenzi P, Bocedi A, Heptonstall J, Capobianchi MR, Di Caro A, Mastrangelo E, Bolognesi M, Ippolito G. Ebolavirus and Marburgvirus: insight the Filoviridae family.. Mol Aspects Med 2008 Jun;29(3):151-85.
- Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.. Nature 2011 Aug 24;477(7364):340-3.
- Jones SM, Feldmann H, Ströher U, Geisbert JB, Fernando L, Grolla A, Klenk HD, Sullivan NJ, Volchkov VE, Fritz EA, Daddario KM, Hensley LE, Jahrling PB, Geisbert TW. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses.. Nat Med 2005 Jul;11(7):786-90.
- Wong G, Audet J, Fernando L, Fausther-Bovendo H, Alimonti JB, Kobinger GP, Qiu X. Immunization with vesicular stomatitis virus vaccine expressing the Ebola glycoprotein provides sustained long-term protection in rodents.. Vaccine 2014 Sep 29;32(43):5722-9.
- Sullivan NJ, Geisbert TW, Geisbert JB, Shedlock DJ, Xu L, Lamoreaux L, Custers JH, Popernack PM, Yang ZY, Pau MG, Roederer M, Koup RA, Goudsmit J, Jahrling PB, Nabel GJ. Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs.. PLoS Med 2006 Jun;3(6):e177.
- Sullivan NJ, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventive vaccine for Ebola virus infection in primates.. Nature 2000 Nov 30;408(6812):605-9.
- Bukreyev A, Rollin PE, Tate MK, Yang L, Zaki SR, Shieh WJ, Murphy BR, Collins PL, Sanchez A. Successful topical respiratory tract immunization of primates against Ebola virus.. J Virol 2007 Jun;81(12):6379-88.
- Blaney JE, Marzi A, Willet M, Papaneri AB, Wirblich C, Feldmann F, Holbrook M, Jahrling P, Feldmann H, Schnell MJ. Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.. PLoS Pathog 2013;9(5):e1003389.
- Shuai L, Wang X, Wen Z, Ge J, Wang J, Zhao D, Bu Z. Genetically modified rabies virus-vectored Ebola virus disease vaccines are safe and induce efficacious immune responses in mice and dogs.. Antiviral Res 2017 Oct;146:36-44.
- Quinn M, Erkes DA, Snyder CM. Cytomegalovirus and immunotherapy: opportunistic pathogen, novel target for cancer and a promising vaccine vector.. Immunotherapy 2016 Feb;8(2):211-21.
- Pushko P, Bray M, Ludwig GV, Parker M, Schmaljohn A, Sanchez A, Jahrling PB, Smith JF. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus.. Vaccine 2000 Aug 15;19(1):142-53.
- Sunay MME, Martins KAO, Steffens JT, Gregory M, Vantongeren SA, Van Hoeven N, Garnes PG, Bavari S. Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice.. Vaccine 2019 Jun 27;37(29):3902-3910.
- Suder E, Furuyama W, Feldmann H, Marzi A, de Wit E. The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials.. Hum Vaccin Immunother 2018;14(9):2107-2113.
- Furuyama W, Marzi A. Ebola Virus: Pathogenesis and Countermeasure Development.. Annu Rev Virol 2019 Sep 29;6(1):435-458.
- Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.. Nature 2014 Oct 2;514(7520):47-53.
- Zheng X, Wong G, Zhao Y, Wang H, He S, Bi Y, Chen W, Jin H, Gai W, Chu D, Cao Z, Wang C, Fan Q, Chi H, Gao Y, Wang T, Feng N, Yan F, Huang G, Zheng Y, Li N, Li Y, Qian J, Zou Y, Kobinger G, Gao GF, Qiu X, Yang S, Xia X. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.. Sci Rep 2016 Apr 12;6:24179.
- Boisgérault F, Morón G, Leclerc C. Virus-like particles: a new family of delivery systems.. Expert Rev Vaccines 2002 Jun;1(1):101-9.
- Näslund J, Lagerqvist N, Habjan M, Lundkvist A, Evander M, Ahlm C, Weber F, Bucht G. Vaccination with virus-like particles protects mice from lethal infection of Rift Valley Fever Virus.. Virology 2009 Mar 15;385(2):409-15.
- Warfield KL, Aman MJ. Advances in virus-like particle vaccines for filoviruses.. J Infect Dis 2011 Nov;204 Suppl 3(Suppl 3):S1053-9.
- Zeltins A. Construction and characterization of virus-like particles: a review.. Mol Biotechnol 2013 Jan;53(1):92-107.
- Ohimain EI. Recent advances in the development of vaccines for Ebola virus disease.. Virus Res 2016 Jan 4;211:174-85.
- Pastor AR, González-Domínguez G, Díaz-Salinas MA, Ramírez OT, Palomares LA. Defining the multiplicity and time of infection for the production of Zaire Ebola virus-like particles in the insect cell-baculovirus expression system.. Vaccine 2019 Nov 8;37(47):6962-6969.
- Medina MF, Kobinger GP, Rux J, Gasmi M, Looney DJ, Bates P, Wilson JM. Lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene transfer in murine lung.. Mol Ther 2003 Nov;8(5):777-89.
- Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O, Siu LY, Shehata MM, Kayed AS, Moatasim Y, Li M, Poon LL, Guan Y, Webby RJ, Ali MA, Peiris JS, Kayali G. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013.. Euro Surveill 2013 Sep 5;18(36):pii=20574.
- Ewer K, Rampling T, Venkatraman N, Bowyer G, Wright D, Lambe T, Imoukhuede EB, Payne R, Fehling SK, Strecker T, Biedenkopf N, Krähling V, Tully CM, Edwards NJ, Bentley EM, Samuel D, Labbé G, Jin J, Gibani M, Minhinnick A, Wilkie M, Poulton I, Lella N, Roberts R, Hartnell F, Bliss C, Sierra-Davidson K, Powlson J, Berrie E, Tedder R, Roman F, De Ryck I, Nicosia A, Sullivan NJ, Stanley DA, Mbaya OT, Ledgerwood JE, Schwartz RM, Siani L, Colloca S, Folgori A, Di Marco S, Cortese R, Wright E, Becker S, Graham BS, Koup RA, Levine MM, Volkmann A, Chaplin P, Pollard AJ, Draper SJ, Ballou WR, Lawrie A, Gilbert SC, Hill AV. A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.. N Engl J Med 2016 Apr 28;374(17):1635-46.
- Marzi A, Engelmann F, Feldmann F, Haberthur K, Shupert WL, Brining D, Scott DP, Geisbert TW, Kawaoka Y, Katze MG, Feldmann H, Messaoudi I. Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates.. Proc Natl Acad Sci U S A 2013 Jan 29;110(5):1893-8.
- Warfield KL, Swenson DL, Olinger GG, Kalina WV, Aman MJ, Bavari S. Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge.. J Infect Dis 2007 Nov 15;196 Suppl 2:S430-7.
- Martins KA, Steffens JT, van Tongeren SA, Wells JB, Bergeron AA, Dickson SP, Dye JM, Salazar AM, Bavari S. Toll-like receptor agonist augments virus-like particle-mediated protection from Ebola virus with transient immune activation.. PLoS One 2014;9(2):e89735.
- Squaiella-Baptistão CC, Magnoli FC, Marcelino JR, Sant'Anna OA, Tambourgi DV. Quality of horse F(ab')(2) antitoxins and anti-rabies immunoglobulins: protein content and anticomplementary activity.. J Venom Anim Toxins Incl Trop Dis 2018;24:16.
- Zhang XJ, Li HL, Deng DY, Ji C, Yao XD, Liu JX. Functional and proteomic comparison of different techniques to produce equine anti-tetanus immunoglobulin F(ab')2 fragments.. J Chromatogr B Analyt Technol Biomed Life Sci 2018 Aug 15;1092:29-39.
- Perry AL, Hayes AJ, Cox HA, Alcock F, Parker AR. Comparison of five commercial anti-tetanus toxoid immunoglobulin G enzyme-linked immunosorbent assays.. Clin Vaccine Immunol 2009 Dec;16(12):1837-9.
Citations
This article has been cited 3 times.- Kheirvari M, Liu H, Tumban E. Virus-like Particle Vaccines and Platforms for Vaccine Development.. Viruses 2023 May 2;15(5).
- Vogel M, Bachmann MF. Special Issue "Virus-Like Particle Vaccines".. Viruses 2020 Aug 10;12(8).
- Eroglu GB, Inan C, Nalcacioglu R, Demirbag Z. Genome sequence analysis of a Helicoverpa armigera single nucleopolyhedrovirus (HearNPV-TR) isolated from Heliothis peltigera in Turkey.. PLoS One 2020;15(6):e0234635.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
