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Antiviral research2015; 116; 27-33; doi: 10.1016/j.antiviral.2015.01.009

Antiserum from mice vaccinated with modified vaccinia Ankara virus expressing African horse sickness virus (AHSV) VP2 provides protection when it is administered 48h before, or 48h after challenge.

Abstract: Previous studies show that a recombinant modified vaccinia Ankara (MVA) virus expressing VP2 of AHSV serotype 4 (MVA-VP2) induced virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR -/-) against challenge. Follow up experiments indicated that passive transfer of antiserum, from MVA-VP2 immune donors to recipient mice 1h before challenge, conferred complete clinical protection and significantly reduced viraemia. These studies have been extended to determine the protective effect of MVA-VP2 vaccine-induced antiserum, when administered 48h before, or 48h after challenge. In addition, passive transfer of splenocytes was undertaken to assess if they confer any degree of immunity to immunologically naïve recipient mice. Thus, antisera and splenocytes were collected from groups of mice that had been vaccinated with MVA-VP2, or wild type MVA (MVA-wt), for passive immunisation of recipient mice. The latter were subsequently challenged with AHSV-4 (together with appropriate vaccinated or unvaccinated control animals) and protection was assessed by comparing clinical signs, lethality and viraemia between treated and control groups. All antiserum recipients showed high protection against disease (100% survival rates even in mice that were immunised 48h after challenge) and statistically significant reduction or viraemia in comparison with the control groups. The mouse group receiving splenocytes from MVA-VP2 vaccinates, showed only a 40% survival rate, with a small reduction in viraemia, compared to those mice that had received splenocytes from MVA-wt vaccinates. These results confirm the primarily humoral nature of protective immunity conferred by MVA-VP2 vaccination and show the potential of administering MVA-VP2 specific antiserum as an emergency treatment for AHSV.
Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
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Publication Date: 2015-01-30 PubMed ID: 25643968PubMed Central: PMC7125940DOI: 10.1016/j.antiviral.2015.01.009Google 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.

The research focuses on the protective effect of the Antiserum from mice vaccinated with recombinant modified vaccinia Ankara (MVA) virus expressing African horse sickness virus (AHSV) VP2, when administered 48 hours before or after exposure to the virus. The results point towards the potential use of MVA-VP2 specific antiserum as an emergency treatment for AHSV.

Aim of The Research

  • The main objective of this research was to understand the protective capability of the Antiserum (antibody-rich fluid) obtained from mice vaccinated with the MVA virus expressing AHSV VP2.
  • The research also aimed to test the protective efficacy of this antiserum, when it is administered either 48 hours before, or 48 hours after the challenge.

Methodology

  • Antisera and splenocytes (white blood cells in the spleen) were collected from two groups of mice – one that had been vaccinated with MVA-VP2 and the other with wild type MVA (MVA-wt).
  • This was followed by passive immunisation of recipient mice, which were then subjected to an AHSV-4 challenge. This group was compared with a control group.

Findings

  • The study found that all antiserum recipients demonstrated strong resistance against the disease, presenting a 100% survival rate, and a significant reduction in viraemia, even when immunised 48 hours after exposure to the virus.
  • The group that received splenocytes from MVA-VP2 vaccinated mice showed a 40% survival rate, with a minor drop in viraemia as compared to mice that received splenocytes from MVA-wt vaccinates. This result underlines the main role of humoral immunity (immunity brought about by antibodies) in the protective immunity offered by MVA-VP2 vaccination.

Conclusion

  • The results of the research established the potential of using MVA-VP2 specific antiserum as an emergency treatment for AHSV, offering new directions for future therapeutics involved in controlling the disease.

Cite This Article

APA
Calvo-Pinilla E, de la Poza F, Gubbins S, Mertens PP, Ortego J, Castillo-Olivares J. (2015). Antiserum from mice vaccinated with modified vaccinia Ankara virus expressing African horse sickness virus (AHSV) VP2 provides protection when it is administered 48h before, or 48h after challenge. Antiviral Res, 116, 27-33. https://doi.org/10.1016/j.antiviral.2015.01.009

Publication

Antiviral research
ISSN: 1872-9096
NlmUniqueID: 8109699
Country: Netherlands
Language: English
Volume: 116
Pages: 27-33

Researcher Affiliations

Calvo-Pinilla, Eva
  • The Pirbright Institute, Pirbright, Woking, Surrey, United Kingdom.
de la Poza, Francisco
  • Centro de Investigación en Sanidad Animal, CISA-INIA, Valdeolmos, Madrid, Spain.
Gubbins, Simon
  • The Pirbright Institute, Pirbright, Woking, Surrey, United Kingdom.
Mertens, Peter Paul Clement
  • The Pirbright Institute, Pirbright, Woking, Surrey, United Kingdom.
Ortego, Javier
  • Centro de Investigación en Sanidad Animal, CISA-INIA, Valdeolmos, Madrid, Spain.
Castillo-Olivares, Javier
  • The Pirbright Institute, Pirbright, Woking, Surrey, United Kingdom. Electronic address: javier.castillo-olivares@pirbright.ac.uk.

MeSH Terms

  • African Horse Sickness / immunology
  • African Horse Sickness / prevention & control
  • African Horse Sickness / therapy
  • African Horse Sickness / virology
  • African Horse Sickness Virus / genetics
  • African Horse Sickness Virus / immunology
  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / immunology
  • Capsid Proteins / immunology
  • Enzyme-Linked Immunospot Assay
  • Horses
  • Immunization, Passive
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Knockout
  • Receptor, Interferon alpha-beta / genetics
  • Spleen / cytology
  • Viral Vaccines / immunology
  • Viral Vaccines / therapeutic use
  • Viremia / prevention & control

Grant Funding

  • BBS/E/I/00001455 / Biotechnology and Biological Sciences Research Council

References

This article includes 35 references
  1. Alberca B, Bachanek-Bankowska K, Cabana M, Calvo-Pinilla E, Viaplana E, Frost L, Gubbins S, Urniza A, Mertens P, Castillo-Olivares J. Vaccination of horses with a recombinant modified vaccinia Ankara virus (MVA) expressing African horse sickness (AHS) virus major capsid protein VP2 provides complete clinical protection against challenge.. Vaccine 2014;32(29):3670–3674.
    pmc: PMC4061461pubmed: 24837765
  2. Bentley L, Fehrsen J, Jordaan F, Huismans H, du Plessis D.H. Identification of antigenic regions on VP2 of African horse sickness virus serotype 3 by using phage-displayed epitope libraries.. J. Gen. Virol. 2000;81(Pt 4):993–1000.
    pubmed: 10725425
  3. Berthoud T.K, Hamill M, Lillie P.J, Hwenda L, Collins K.A, Ewer K.J, Milicic A, Poyntz H.C, Lambe T, Fletcher H.A, Hill A.V, Gilbert S.C. Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1.. Clin. Infect. Dis. 2011;52(1):1–7.
    pmc: PMC3060888pubmed: 21148512
  4. Blackburn N.K, Swanepoel R. Observations on antibody levels associated with active and passive immunity to African horse sickness.. Trop. Anim. Health Prod. 1988;20(4):203–210.
    pubmed: 3238767
  5. Burrage T.G, Trevejo R, Stone-Marschat M, Laegreid W.W. Neutralizing epitopes of African horse sickness virus serotype 4 are located on VP2.. Virology 1993;196(2):799–803.
    pubmed: 7690505
  6. Calvo-Pinilla E, de la Poza F, Gubbins S, Mertens P.P, Ortego J, Castillo-Olivares J. Vaccination of mice with a modified Vaccinia Ankara (MVA) virus expressing the African horse sickness virus (AHSV) capsid protein VP2 induces virus neutralising antibodies that confer protection against AHSV upon passive immunisation.. Virus Res. 2014;180:23–30.
    pubmed: 24333835
  7. Calvo-Pinilla E, Rodriguez-Calvo T, Sevilla N, Ortego J. Heterologous prime boost vaccination with DNA and recombinant modified vaccinia virus Ankara protects IFNAR(−/−) mice against lethal bluetongue infection.. Vaccine 2009;28(2):437–445.
    pubmed: 19857449
  8. Castillo-Olivares J, Calvo-Pinilla E, Casanova I, Bachanek-Bankowska K, Chiam R, Maan S, Nieto J.M, Ortego J, Mertens P.P. A modified vaccinia Ankara virus (MVA) vaccine expressing African horse sickness virus (AHSV) VP2 protects against AHSV challenge in an IFNAR −/− mouse model.. PLoS One 2011;6(1):e16503.
    pmc: PMC3027694pubmed: 21298069
  9. Cosma A, Nagaraj R, Buhler S, Hinkula J, Busch D.H, Sutter G, Goebel F.D, Erfle V. Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals.. Vaccine 2003;22(1):21–29.
    pubmed: 14604567
  10. Crafford J.E, Lourens C.W, Gardner I.A, Maclachlan N.J, Guthrie A.J. Passive transfer and rate of decay of maternal antibody against African horse sickness virus in South African thoroughbred foals.. Equine Vet. J. 2013;45(5):604–607.
    pubmed: 23294121
  11. Chen H, Hou J, Jiang X, Ma S, Meng M, Wang B, Zhang M, Tang X, Zhang F, Wan T, Li N, Yu Y, Hu H, Yang R, He W, Wang X, Cao X. Response of memory CD8+ T cells to severe acute respiratory syndrome (SARS) coronavirus in recovered SARS patients and healthy individuals.. J. Immunol. 2005;175(1):591–598.
    pubmed: 15972696
  12. Chiam R, Sharp E, Maan S, Rao S, Mertens P, Blacklaws B, Davis-Poynter N, Wood J, Castillo-Olivares J. Induction of antibody responses to African horse sickness virus (AHSV) in ponies after vaccination with recombinant modified vaccinia Ankara (MVA). PLoS One 2009;4(6):e5997.
    pmc: PMC2694985pubmed: 19543394
  13. de la Poza F, Calvo-Pinilla E, Lopez-Gil E, Marin-Lopez A, Mateos F, Castillo-Olivares J, Lorenzo G, Ortego J. Ns1 is a key protein in the vaccine composition to protect Ifnar(-/-) mice against infection with multiple serotypes of African horse sickness virus.. PloS one 2013;8:e70197.
    pmc: PMC3720900pubmed: 23894615
  14. Draper S.J, Cottingham M.G, Gilbert S.C. Utilizing poxviral vectored vaccines for antibody induction-progress and prospects.. Vaccine 2013;31(39):4223–4230.
    pmc: PMC7131268pubmed: 23746455
  15. El Garch H, Crafford J.E, Amouyal P, Durand P.Y, Edlund Toulemonde C, Lemaitre L, Cozette V, Guthrie A, Minke J.M. An African horse sickness virus serotype 4 recombinant canarypox virus vaccine elicits specific cell-mediated immune responses in horses.. Vet. Immunol. Immunopathol. 2012;149(1–2):76–85.
    pubmed: 22763149
  16. Garcia-Arriaza J, Cepeda V, Hallengard D, Sorzano C.O, Kummerer B.M, Liljestrom P, Esteban M. A novel poxvirus-based vaccine, MVA-CHIKV, is highly immunogenic and protects mice against chikungunya infection.. J. Virol. 2014;88(6):3527–3547.
    pmc: PMC3957920pubmed: 24403588
  17. Gilbert S.C. Clinical development of modified vaccinia virus Ankara vaccines.. Vaccine 2013;31(39):4241–4246.
    pubmed: 23523410
  18. Gomez C.E, Najera J.L, Krupa M, Esteban M. The poxvirus vectors MVA and NYVAC as gene delivery systems for vaccination against infectious diseases and cancer.. Curr. Gene Ther. 2008;8:97–120.
    pubmed: 18393831
  19. Jabbar T.K, Calvo-Pinilla E, Mateos F, Gubbins S, Bin-Tarif A, Bachanek-Bankowska K, Alpar O, Ortego J, Takamatsu H.H, Mertens P.P, Castillo-Olivares J. Protection of IFNAR (−/−) mice against bluetongue virus serotype 8, by heterologous (DNA/rMVA) and homologous (rMVA/rMVA) vaccination, expressing outer-capsid protein VP2.. PLoS One 2013;8(4):e60574.
    pmc: PMC3625202pubmed: 23593251
  20. Jeggo M.H, Wardley R.C, Brownlie J. A study of the role of cell-mediated immunity in bluetongue virus infection in sheep, using cellular adoptive transfer techniques.. Immunology 1984;52(3):403–410.
    pmc: PMC1454488pubmed: 6086501
  21. Jeggo M.H, Wardley R.C, Taylor W.P. Role of neutralising antibody in passive immunity to bluetongue infection.. Res. Vet. Sci. 1984;36(1):81–86.
    pubmed: 6324311
  22. Karber G. 50% end-point calculation.. Arch. Exp. Pathol. Pharmak. 1931;162:480–483.
  23. Kreijtz J.H, Suezer Y, de Mutsert G, van Amerongen G, Schwantes A, van den Brand J.M, Fouchier R.A, Lower J, Osterhaus A.D, Sutter G, Rimmelzwaan G.F. MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.. PLoS One 2009;4(11):e7790.
    pmc: PMC2771904pubmed: 19915662
  24. Martinez-Torrecuadrada J.L, Casal J.I. Identification of a linear neutralization domain in the protein VP2 of African horse sickness virus.. Virology 1995;210(2):391–399.
    pubmed: 7542417
  25. Martinez-Torrecuadrada J.L, Diaz-Laviada M, Roy P, Sanchez C, Vela C, Sanchez-Vizcaino J.M, Casal J.I. Full protection against African horse sickness (AHS) in horses induced by baculovirus-derived AHS virus serotype 4 VP2, VP5 and VP7.. J. Gen. Virol. 1996;77(Pt 6):1211–1221.
    pubmed: 8683209
  26. Martinez-Torrecuadrada J.L, Langeveld J.P, Meloen R.H, Casal J.I. Definition of neutralizing sites on African horse sickness virus serotype 4 VP2 at the level of peptides.. J. Gen. Virol. 2001;82(Pt 10):2415–2424.
    pubmed: 11562535
  27. Mellor P.S, Hamblin C. African horse sickness.. Vet. Res. 2004;35(4):445–466.
    pubmed: 15236676
  28. Ogwang C, Afolabi M, Kimani D, Jagne Y.J, Sheehy S.H, Bliss C.M, Duncan C.J, Collins K.A, Garcia Knight M.A, Kimani E, Anagnostou N.A, Berrie E, Moyle S, Gilbert S.C, Spencer A.J, Soipei P, Mueller J, Okebe J, Colloca S, Cortese R, Viebig N.K, Roberts R, Gantlett K, Lawrie A.M, Nicosia A, Imoukhuede E.B, Bejon P, Urban B.C, Flanagan K.L, Ewer K.J, Chilengi R, Hill A.V, Bojang K. Safety and immunogenicity of heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults.. PLoS One 2013;8(3):e57726.
    pmc: PMC3602521pubmed: 23526949
  29. Pretorius A, Van Kleef M, Van Wyngaardt W, Heath J. Virus-specific CD8(+) T-cells detected in PBMC from horses vaccinated against African horse sickness virus.. Vet. Immunol. Immunopathol. 2012;146(1):81–86.
    pubmed: 22365333
  30. Ramirez J.C, Gherardi M.M, Rodriguez D, Esteban M. Attenuated modified vaccinia virus Ankara can be used as an immunizing agent under conditions of preexisting immunity to the vector.. J. Virol. 2000;74(16):7651–7655.
    pmc: PMC112288pubmed: 10906221
  31. Romito M, Du Plessis D.H, Viljoen G.J. Immune responses in a horse inoculated with the VP2 gene of African horse sickness virus.. Onderstepoort J. Vet. Res. 1999;66(2):139–144.
    pubmed: 10486832
  32. Roy P, Mertens P.P, Casal I. African horse sickness virus structure.. Comp. Immunol. Microbiol. Infect. Dis. 1994;17(3–4):243–273.
    pubmed: 8001348
  33. Roy P, Sutton G. New generation of African horse sickness virus vaccines based on structural and molecular studies of the virus particles.. Arch. Virol. Suppl. 1998;14:177–202.
    pubmed: 9785506
  34. Scanlen M, Paweska J.T, Verschoor J.A, van Dijk A.A. The protective efficacy of a recombinant VP2-based African horse sickness subunit vaccine candidate is determined by adjuvant.. Vaccine 2002;20(7–8):1079–1088.
    pubmed: 11803068
  35. Stone-Marschat M.A, Moss S.R, Burrage T.G, Barber M.L, Roy P, Laegreid W.W. Immunization with VP2 is sufficient for protection against lethal challenge with African horse sickness virus Type 4.. Virology 1996;220(1):219–222.
    pubmed: 8659117

Citations

This article has been cited 16 times.
  1. O'Kennedy MM, Roth R, Ebersohn K, du Plessis LH, Mamputha S, Rutkowska DA, du Preez I, Verschoor JA, Lemmer Y. Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice. PLoS One 2024;19(4):e0301340.
    doi: 10.1371/journal.pone.0301340pubmed: 38625924google scholar: lookup
  2. Migné CV, Heckmann A, Monsion B, Mohd Jaafar F, Galon C, Rakotobe S, Bell-Sakyi L, Moutailler S, Attoui H. Age- and Sex-Associated Pathogenesis of Cell Culture-Passaged Kemerovo Virus in IFNAR((-/-)) Mice. Int J Mol Sci 2024 Mar 9;25(6).
    doi: 10.3390/ijms25063177pubmed: 38542150google scholar: lookup
  3. Calvo-Pinilla E, Jiménez-Cabello L, Utrilla-Trigo S, Illescas-Amo M, Ortego J. Cytokine mRNA Expression Profile in Target Organs of IFNAR (-/-) Mice Infected with African Horse Sickness Virus. Int J Mol Sci 2024 Feb 8;25(4).
    doi: 10.3390/ijms25042065pubmed: 38396742google scholar: lookup
  4. Mohd Jaafar F, Belhouchet M, Monsion B, Bell-Sakyi L, Mertens PPC, Attoui H. Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses. Viruses 2023 Sep 12;15(9).
    doi: 10.3390/v15091908pubmed: 37766314google scholar: lookup
  5. Attoui H, Mohd Jaafar F, Monsion B, Klonjkowski B, Reid E, Fay PC, Saunders K, Lomonossoff G, Haig D, Mertens PPC. Increased Clinical Signs and Mortality in IFNAR((-/-)) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype. Pathogens 2023 Apr 15;12(4).
    doi: 10.3390/pathogens12040602pubmed: 37111488google scholar: lookup
  6. Jones LM, Hawes PC, Salguero FJ, Castillo-Olivares J. Pathological features of African horse sickness virus infection in IFNAR(-/-) mice. Front Vet Sci 2023;10:1114240.
    doi: 10.3389/fvets.2023.1114240pubmed: 37065248google scholar: lookup
  7. Mohd Jaafar F, Monsion B, Belhouchet M, Mertens PPC, Attoui H. Inhibition of Orbivirus Replication by Fluvastatin and Identification of the Key Elements of the Mevalonate Pathway Involved. Viruses 2021 Jul 23;13(8).
    doi: 10.3390/v13081437pubmed: 34452303google scholar: lookup
  8. Castillo-Olivares J. African horse sickness in Thailand: Challenges of controlling an outbreak by vaccination. Equine Vet J 2021 Jan;53(1):9-14.
    doi: 10.1111/evj.13353pubmed: 33007121google scholar: lookup
  9. Calvo-Pinilla E, Marín-López A, Utrilla-Trigo S, Jiménez-Cabello L, Ortego J. Reverse genetics approaches: a novel strategy for African horse sickness virus vaccine design. Curr Opin Virol 2020 Oct;44:49-56.
    doi: 10.1016/j.coviro.2020.06.003pubmed: 32659516google scholar: lookup
  10. Dennis SJ, Meyers AE, Hitzeroth II, Rybicki EP. African Horse Sickness: A Review of Current Understanding and Vaccine Development. Viruses 2019 Sep 11;11(9).
    doi: 10.3390/v11090844pubmed: 31514299google scholar: lookup
  11. Marín-Lopez A, Calvo-Pinilla E, Moreno S, Utrilla-Trigo S, Nogales A, Brun A, Fikrig E, Ortego J. Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor. Viruses 2019 Jan 8;11(1).
    doi: 10.3390/v11010035pubmed: 30625992google scholar: lookup
  12. Aksular M, Calvo-Pinilla E, Marín-López A, Ortego J, Chambers AC, King LA, Castillo-Olivares J. A single dose of African horse sickness virus (AHSV) VP2 based vaccines provides complete clinical protection in a mouse model. Vaccine 2018 Nov 12;36(46):7003-7010.
    doi: 10.1016/j.vaccine.2018.09.065pubmed: 30309744google scholar: lookup
  13. Marín-López A, Calvo-Pinilla E, Barriales D, Lorenzo G, Brun A, Anguita J, Ortego J. CD8 T Cell Responses to an Immunodominant Epitope within the Nonstructural Protein NS1 Provide Wide Immunoprotection against Bluetongue Virus in IFNAR(-/-) Mice. J Virol 2018 Aug 15;92(16).
    doi: 10.1128/JVI.00938-18pubmed: 29875250google scholar: lookup
  14. Calvo-Pinilla E, Gubbins S, Mertens P, Ortego J, Castillo-Olivares J. The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host. Antiviral Res 2018 Jun;154:132-139.
    doi: 10.1016/j.antiviral.2018.04.015pubmed: 29678552google scholar: lookup
  15. Dennis SJ, Meyers AE, Guthrie AJ, Hitzeroth II, Rybicki EP. Immunogenicity of plant-produced African horse sickness virus-like particles: implications for a novel vaccine. Plant Biotechnol J 2018 Feb;16(2):442-450.
    doi: 10.1111/pbi.12783pubmed: 28650085google scholar: lookup
  16. Mathebula EM, Faber FE, Van Wyngaardt W, Van Schalkwyk A, Pretorius A, Fehrsen J. B-cell epitopes of African horse sickness virus serotype 4 recognised by immune horse sera. Onderstepoort J Vet Res 2017 Feb 24;84(1):e1-e12.
    doi: 10.4102/ojvr.v84i1.1313pubmed: 28281773google scholar: lookup
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