FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Antiviral Res / Development of horse neutralizing immunoglobulin and immunog...
Antiviral research2019; 174; 104666; doi: 10.1016/j.antiviral.2019.104666

Development of horse neutralizing immunoglobulin and immunoglobulin fragments against Junín virus.

Abstract: Argentine haemorrhagic fever (AHF) is a rodent-borne disease with a lethality as high as ~30%, which is caused by the New World arenavirus, Junín virus (JUNV). It was once a major epidemic in South America and puts millions of people in Argentina at risk. Here, we aimed to develop horse antibodies or antibody fragments against JUNV. Before preparing the horse antibodies, a strategy to efficiently generate horse antisera was established based on comparisons among immunogens and immunization methods in both mice and horses. Antisera against JUNV were finally obtained by vaccinating horses with vesicular stomatitis virus pseudotypes bearing JUNV GP. The horse antibodies IgG and F(ab')2 were subsequently demonstrated to effectively neutralize vesicular stomatitis virus pseudotypes bearing JUNV GP and to show some cross-neutralization against pathogenic New World arenaviruses. Further research revealed that Asp123 on GP1 is an important site for the binding of antibodies targeting mainly JUNV GP1 for neutralization. Collectively, this study presents an efficient strategy to develop horse antisera against JUNV and provides GP1-specific horse antibodies as potential therapeutics for AHF.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
Get Full Text
Publication Date: 2019-11-21 PubMed ID: 31760108PubMed Central: PMC7114285DOI: 10.1016/j.antiviral.2019.104666Google 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.
LinkedInCopy
  • 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 study aimed to develop horse antibodies against Junín virus (JUNV), which causes the potentially lethal Argentine haemorrhagic fever (AHF). Researchers established an effective method to generate horse antibodies, demonstrated their capacity to neutralize JUNV, and identified a key binding site on the virus’s GP1 protein.

Development of Horse Antibodies Against Junín Virus

  • The research aimed at developing horse antibodies that could treat or combat Argentine Hemorrhagic Fever (AHF), a potentially deadly disease caused by the Junín virus. This virus, mainly spreading through rodents, had caused major epidemics in South America and still poses a threat to millions of people in Argentina.
  • Before commencing the process of preparing horse antibodies, the researchers set up a strategy to create horse antisera efficiently. This strategy was designed based on comparisons among immunogens and immunization practices in both mice and horses.

Methodology and Findings

  • The research team used vesicular stomatitis virus pseudotypes bearing the Junín virus GP to vaccinate horses, subsequently obtaining antisera against the virus.
  • They later tested the “IgG” and “F(ab’)” horse antibodies obtained from the antisera and found that these could effectively neutralize the vesicular stomatitis virus pseudotypes bearing the Junín virus GP.
  • In the process, the antibodies also exhibited some cross-neutralization properties against other pathogenic New World arenaviruses.

Identification of Key Binding Site

  • The research took a step further by identifying an essential site on GP1, a protein associated with the Junín virus, which the antibodies target for neutralization. This vital site was identified as Asp123.
  • Understanding the specific binding site can prove critical in designing and strategizing therapeutic interventions targeting the Junín virus.

Conclusion of the Study

  • The study delivered an efficient method of developing horse antisera against the Junín virus and potentially other similar viruses.
  • The discovery of GP1-specific horse antibodies with their known binding site sets the stage for these to be used as potential therapeutics in the treatment of AHF.

Cite This Article

APA
Pan X, Wu Y, Wang W, Zhang L, Xiao G. (2019). Development of horse neutralizing immunoglobulin and immunoglobulin fragments against Junín virus. Antiviral Res, 174, 104666. https://doi.org/10.1016/j.antiviral.2019.104666

Publication

Antiviral research
ISSN: 1872-9096
NlmUniqueID: 8109699
Country: Netherlands
Language: English
Volume: 174
Pages: 104666

Researcher Affiliations

Pan, Xiaoyan
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
Wu, Yan
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
Wang, Wei
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100039, China.
Zhang, Leike
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100039, China.
Xiao, Gengfu
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100039, China. Electronic address: xiaogf@wh.iov.cn.

MeSH Terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cross Reactions
  • Female
  • Hemorrhagic Fever, American / immunology
  • Hemorrhagic Fever, American / veterinary
  • Horses / immunology
  • Immunoglobulin Fragments / immunology
  • Junin virus / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests

Conflict of Interest Statement

Declaration of competing interest The authors declare no competing financial interests.

References

This article includes 38 references
  1. Amanat F, Duehr J, Oestereich L, Hastie K.M, Ollmann Saphire E, Krammer F. Antibodies to the glycoprotein GP2 subunit cross-react between old and New World arenaviruses.. mSphere 2018;3 e00189-00118.
    pmc: PMC5932378pubmed: 29720525
  2. Chung K.M, Nybakken G.E, Thompson B.S, Engle M.J, Marri A, Fremont D.H, Diamond M.S. Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and -independent mechanisms.. J. Virol. 2006;80:1340–1351.
    pmc: PMC1346945pubmed: 16415011
  3. Clark L.E, Mahmutovic S, Raymond D.D, Dilanyan T, Koma T, Manning J.T, Shankar S, Levis S.C, Briggiler A.M, Enria D.A, Wucherpfennig K.W, Paessler S, Abraham J. Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses.. Nat. Commun. 2018;9:1884.
    pmc: PMC5951886pubmed: 29760382
  4. Cui J, Zhao Y, Wang H, Qiu B, Cao Z, Li Q, Zhang Y, Yan F, Jin H, Wang T, Sun W, Feng N, Gao Y, Sun J, Wang Y, Perlman S, Zhao J, Yang S, Xia X. Equine immunoglobulin and equine neutralizing F(ab')(2) protect mice from West Nile virus infection.. Viruses 2016;8:e332.
    pmc: PMC5192393pubmed: 27999340
  5. Enria D.A, Briggiler A.M, Sanchez Z. Treatment of Argentine hemorrhagic fever.. Antivir. Res. 2008;78:132–139.
    pmc: PMC7144853pubmed: 18054395
  6. Garbutt M, Liebscher R, Wahl-Jensen V, Jones S, Moller P, Wagner R, Volchkov V, Klenk H.D, Feldmann H, Stroher U. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses.. J. Virol. 2004;78:5458–5465.
    pmc: PMC400370pubmed: 15113924
  7. Golden J.W, Maes P, Kwilas S.A, Ballantyne J, Hooper J.W. Glycoprotein-specific antibodies produced by DNA vaccination protect Guinea pigs from lethal Argentine and Venezuelan hemorrhagic fever.. J. Virol. 2016;90:3515–3529.
    pmc: PMC4794662pubmed: 26792737
  8. Gonzalez J.P, Emonet S, de Lamballerie X, Charrel R. Arenaviruses.. Curr. Top. Microbiol. Immunol. 2007;315:253–288.
    pmc: PMC7122678pubmed: 17848068
  9. Gonzalez J.P, Souris M, Valdivia-Granda W. Global spread of hemorrhagic fever viruses: predicting pandemics.. Methods Mol. Biol. 2018;1604:3–31.
    pmc: PMC7120037pubmed: 28986822
  10. Grunwald T, Ulbert S. Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases.. Clin. Exp. Vaccine Res. 2015;4:1–10.
    pmc: PMC4313101pubmed: 25648133
  11. Guidolin F.R, Caricati C.P, Marcelino J.R, da Silva W.D. Development of equine IgG antivenoms against major snake groups in Mozambique.. PLoS Neglected Trop. Dis. 2016;10.
    pmc: PMC4701360pubmed: 26730709
  12. Kenyon R.H, Condie R.M, Jahrling P.B, Peters C.J. Protection of Guinea pigs against experimental Argentine hemorrhagic fever by purified human IgG: importance of elimination of infected cells.. Microb. Pathog. 1990;9:219–226.
    pubmed: 1965845
  13. Linero F, Sepulveda C, Christopoulou I, Hulpiau P, Scolaro L, Saelens X. Neutralization of Junin virus by single domain antibodies targeted against the nucleoprotein.. Sci. Rep. 2018;8:11451.
    pmc: PMC6065417pubmed: 30061671
  14. Lu J, Guo Z, Pan X, Wang G, Zhang D, Li Y, Tan B, Ouyang L, Yu X. Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab')2 in mice.. Respir. Res. 2006;7:43.
    pmc: PMC1459145pubmed: 16553963
  15. Lu J.H, Guo Z.M, Han W.Y, Wang G.L, Zhang D.M, Wang Y.F, Sun S.Y, Yang Q.H, Zheng H.Y, Wong B.L, Zhong N.S. Preparation and development of equine hyperimmune globulin F(ab')2 against severe acute respiratory syndrome coronavirus.. Acta Pharmacol. Sin. 2005;26:1479–1484.
    pmc: PMC7091834pubmed: 16297347
  16. Mahmutovic S, Clark L, Levis S.C, Briggiler A.M, Enria D.A, Harrison S.C, Abraham J. Molecular basis for antibody-mediated neutralization of New World hemorrhagic fever mammarenaviruses.. Cell Host Microbe 2015;18:705–713.
    pmc: PMC4685251pubmed: 26651946
  17. Maiztegui J.I, McKee K.T. Jr., Barrera Oro J.G, Harrison L.H, Gibbs P.H, Feuillade M.R, Enria D.A, Briggiler A.M, Levis S.C, Ambrosio A.M, Halsey N.A, Peters C.J. Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group.. J. Infect. Dis. 1998;177:277–283.
    pubmed: 9466512
  18. McLay L, Liang Y, Ly H. Comparative analysis of disease pathogenesis and molecular mechanisms of New World and Old World arenavirus infections.. J. Gen. Virol. 2014;95:1–15.
    pmc: PMC4093776pubmed: 24068704
  19. Mehlhop E, Nelson S, Jost C.A, Gorlatov S, Johnson S, Fremont D.H, Diamond M.S, Pierson T.C. Complement protein C1q reduces the stoichiometric threshold for antibody-mediated neutralization of West Nile virus.. Cell Host Microbe 2009;6:381–391.
    pmc: PMC2782387pubmed: 19837377
  20. Nunberg J.H, York J. The curious case of arenavirus entry, and its inhibition.. Viruses 2012;4:83–101.
    pmc: PMC3280523pubmed: 22355453
  21. Paessler S, Walker D.H. Pathogenesis of the viral hemorrhagic fevers.. Annu. Rev. Pathol. 2013;8:411–440.
    pubmed: 23121052
  22. Pan X, Wu Y, Wang W, Zhang L, Xiao G. Novel neutralizing monoclonal antibodies against Junin virus.. Antivir. Res. 2018;156:21–28.
    pubmed: 29870772
  23. Pontremoli C, Forni D, Sironi M. Arenavirus genomics: novel insights into viral diversity, origin, and evolution.. Curr. Opin. Virol. 2018;34:18–28.
    pubmed: 30497052
  24. Radoshitzky S.R, Abraham J, Spiropoulou C.F, Kuhn J.H, Nguyen D, Li W, Nagel J, Schmidt P.J, Nunberg J.H, Andrews N.C, Farzan M, Choe H. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses.. Nature 2007;446:92–96.
    pmc: PMC3197705pubmed: 17287727
  25. Radoshitzky S.R, Kuhn J.H, Spiropoulou C.F, Albarino C.G, Nguyen D.P, Salazar-Bravo J, Dorfman T, Lee A.S, Wang E, Ross S.R, Choe H, Farzan M. Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses.. Proc. Natl. Acad. Sci. U. S. A. 2008;105:2664–2669.
    pmc: PMC2268193pubmed: 18268337
  26. Ratanabanangkoon K, Tan K.Y, Eursakun S, Tan C.H, Simsiriwong P, Pamornsakda T, Wiriyarat W, Klinpayom C, Tan N.H. A simple and novel strategy for the production of a pan-specific antiserum against elapid snakes of Asia.. PLoS Neglected Trop. Dis. 2016;10.
    pmc: PMC4825939pubmed: 27058956
  27. Ruggiero H.A, Perez Isquierdo F, Milani H.A, Barri A, Val A, Maglio F, Astarloa L, Gonzalez Cambaceres C, Milani H.L, Tallone J.C. Treatment of Argentine hemorrhagic fever with convalescent's plasma. 4433 cases.. Presse Med. 1986;15:2239–2242.
    pubmed: 2949253
  28. Saade F, Petrovsky N. Technologies for enhanced efficacy of DNA vaccines.. Expert Rev. Vaccines 2012;11:189–209.
    pmc: PMC3293989pubmed: 22309668
  29. Wang H, Wong G, Zhu W, He S, Zhao Y, Yan F, Rahim M.N, Bi Y, Zhang Z, Cheng K, Jin H, Cao Z, Zheng X, Gai W, Bai J, Chen W, Zou Y, Gao Y, Gao G.F, Yang S, Xia X, Qiu X. Equine-origin immunoglobulin fragments protects nonhuman primates from Ebola virus disease.. J. Virol. 2018;93.
    pmc: PMC6384060pubmed: 30541860
  30. Wang P, Liu Y, Zhang G, Wang S, Guo J, Cao J, Jia X, Zhang L, Xiao G, Wang W. Screening and identification of Lassa virus entry inhibitors from an FDA-approved drug library.. J. Virol. 2018;92 e00954-00918.
    pmc: PMC6069169pubmed: 29899092
  31. Wang W, Zhou Z, Zhang L, Wang S, Xiao G. Structure-function relationship of the mammarenavirus envelope glycoprotein.. Virol. Sin. 2016;31:380–394.
    pmc: PMC8193374pubmed: 27562602
  32. Whitt M.A. Generation of VSV pseudotypes using recombinant DeltaG-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines.. J. Virol. Methods. 2010;169:365–374.
    pmc: PMC2956192pubmed: 20709108
  33. Yu F, Song H, Wu Y, Chang S.Y, Wang L, Li W, Hong B, Xia S, Wang C, Khurana S, Feng Y, Wang Y, Sun Z, He B, Hou D, Manischewitz J, King L.R, Song Y, Min J.Y, Golding H, Ji X, Lu L, Jiang S, Dimitrov D.S, Ying T. A potent germline-like human monoclonal antibody targets a pH-sensitive epitope on H7N9 influenza hemagglutinin.. Cell Host Microbe 2017;22:471–483. e475.
    pmc: PMC6290738pubmed: 28966056
  34. Yu H, Shaffer J.G, Boisen M.L, Hartnett J.N, Zandonatti M.A, Rowland M.M, Heinrich M.L, Martinez-Sobrido L, Cheng B, de la Torre J.C, Andersen K.G, Goba A, Momoh M, Fullah M, Gbakie M, Kanneh L, Koroma V.J, Fonnie R, Jalloh S.C, Kargbo B, Vandi M.A, Gbetuwa M, Ikponmwosa O, Asogun D.A, Okokhere P.O, Follarin O.A, Schieffelin J.S, Pitts K.R, Geisbert J.B, Kulakoski P.C, Wilson R.B, Happi C.T, Sabeti P.C, Gevao S.M, Khan S.H, Grant D.S, Geisbert T.W, Saphire E.O, Branco L.M, Garry R.F. Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits.. Nat. Commun. 2016;10:11544.
    pmc: PMC4866400pubmed: 27161536
  35. Zeitlin L, Geisbert J.B, Deer D.J, Fenton K.A, Bohorov O, Bohorova N, Goodman C, Kim D, Hiatt A, Pauly M.H, Velasco J, Whaley K.J, Altmann F, Gruber C, Steinkellner H, Honko A.N, Kuehne A.I, Aman M.J, Sahandi S, Enterlein S, Zhan X, Enria D, Geisbert T.W. Monoclonal antibody therapy for Junin virus infection.. Proc. Natl. Acad. Sci. U. S. A. 2016;113:4458–4463.
    pmc: PMC4843420pubmed: 27044104
  36. Zeltina A, Krumm S.A, Sahin M, Struwe W.B, Harlos K, Nunberg J.H, Crispin M, Pinschewer D.D, Doores K.J, Bowden T.A. Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization.. Proc. Natl. Acad. Sci. U. S. A. 2017;114:7031–7036.
    pmc: PMC5502616pubmed: 28630325
  37. Zhao Y, Wang C, Qiu B, Li C, Wang H, Jin H, Gai W, Zheng X, Wang T, Sun W, Yan F, Gao Y, Wang Q, Yan J, Chen L, Perlman S, Zhong N, Zhao J, Yang S, Xia X. Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model.. Antivir. Res. 2017;137:125–130.
    pmc: PMC7113855pubmed: 27890674
  38. 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 G.F, Qiu X, Yang S, Xia X. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.. Sci. Rep. 2016;6:24179.
    pmc: PMC4828711pubmed: 27067649
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.