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Pathogens (Basel, Switzerland)2024; 13(6); 458; doi: 10.3390/pathogens13060458

The Potential of Plant-Produced Virus-like Particle Vaccines for African Horse Sickness and Other Equine Orbiviruses.

Abstract: African horse sickness is a devastating viral disease of equids. It is transmitted by biting midges of the genus with mortalities reaching over 90% in naïve horses. It is endemic to sub-Saharan Africa and is seasonally endemic in many parts of southern Africa. However, outbreaks in Europe and Asia have occurred that caused significant economic issues. There are attenuated vaccines available for control of the virus but concerns regarding the safety and efficacy means that alternatives are sought. One promising alternative is the use of virus-like particles in vaccine preparations, which have the potential to be safer and more efficacious as vaccines against African horse sickness. These particles are best made in a complex, eukaryotic system, but due to technical challenges, this may cause significant economic strain on the developing countries most affected by the disease. Therefore, this review also summarises the success so far, and potential, of recombinant protein expression in plants to reduce the economic strain of production.
Publication Date: 2024-05-28 PubMed ID: 38921755PubMed Central: PMC11206403DOI: 10.3390/pathogens13060458Google Scholar: Lookup
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  • Journal Article
  • Review

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.

Overview

  • This article reviews the potential of using plant-produced virus-like particle (VLP) vaccines as a safer and more effective alternative for controlling African horse sickness (AHS), a deadly viral disease affecting horses.
  • It highlights the economic and technical challenges involved, particularly in developing countries, and discusses advances in recombinant protein expression in plants to make vaccine production more affordable.

Background on African Horse Sickness (AHS)

  • AHS is a viral disease primarily affecting equids (horses, donkeys, zebras), caused by the African horse sickness virus (AHSV), an orbivirus.
  • The virus is spread by biting midges of the genus Culicoides, leading to severe disease with mortality rates exceeding 90% in horses with no prior immunity.
  • The disease is endemic to sub-Saharan Africa and exhibits seasonal outbreaks, particularly in southern Africa.
  • Outbreaks outside Africa, in Europe and Asia, have caused major economic losses due to livestock deaths and imposed trade restrictions.

Current Vaccination Approaches and Limitations

  • Live attenuated vaccines currently exist and have been used to control AHS in endemic regions.
  • However, these vaccines raise safety concerns, including the risk of reversion to virulence or causing adverse reactions.
  • They may also have limitations related to efficacy, especially in diverse viral strains or under certain environmental conditions.
  • Such safety and efficacy issues motivate the search for improved vaccine strategies.

Virus-Like Particles (VLPs) as Vaccine Candidates

  • VLPs are self-assembled structures that mimic the virus’s outer shell but lack genetic material, making them non-infectious.
  • Because they resemble natural viruses, VLPs can induce strong immune responses without the risk of causing disease.
  • These particles are recognized as a promising alternative to conventional vaccines for AHS, potentially offering enhanced safety and efficacy.
  • Production of VLPs generally requires complex eukaryotic expression systems to ensure proper protein folding and post-translational modifications.

Challenges in Production and Economic Impact

  • Traditional production systems for VLPs, such as insect or mammalian cell cultures, involve sophisticated technology, high operational costs, and infrastructure challenges.
  • These barriers are significant for many of the countries most affected by AHS, often with limited resources and funding for large-scale vaccine manufacturing.
  • The economic strain makes it difficult to produce and distribute these novel vaccines widely and affordably throughout endemic regions.

Plant-Based Recombinant Protein Expression as a Solution

  • The review highlights the use of plants as biofactories for producing recombinant proteins, including VLPs.
  • Plants offer several advantages: low production costs, ease of scaling up, reduced risk of contamination with human pathogens, and simpler storage requirements.
  • Techniques such as transient expression using agroinfiltration allow rapid and high-yield production of complex proteins and VLPs in plants.
  • Previous research demonstrates successful expression of orbivirus proteins and assembly of VLPs in plants, validating this platform’s potential.
  • Using plant systems could significantly reduce the economic barriers to vaccine development and accessibility in resource-limited settings.

Conclusions and Future Directions

  • Plant-produced VLP vaccines represent a promising avenue to improve the control of African horse sickness by offering safer, effective, and affordable immunization options.
  • Further research and development are needed to optimize expression systems, validate immunogenicity and protective efficacy in horses, and develop scalable manufacturing protocols.
  • If successfully translated into practical vaccines, this approach could benefit not only AHS control but also vaccines targeting other equine orbiviruses.
  • The study advocates for greater investment in plant biotechnology platforms as a strategic tool to address animal health challenges in developing regions.

Cite This Article

APA
Pitchers KG, Boakye OD, Campeotto I, Daly JM. (2024). The Potential of Plant-Produced Virus-like Particle Vaccines for African Horse Sickness and Other Equine Orbiviruses. Pathogens, 13(6), 458. https://doi.org/10.3390/pathogens13060458

Publication

ISSN: 2076-0817
NlmUniqueID: 101596317
Country: Switzerland
Language: English
Volume: 13
Issue: 6
PII: 458

Researcher Affiliations

Pitchers, Kieran G
  • One Virology, School of Veterinary Medicine and Science, Sutton Bonington, University of Nottingham, Nottinghamshire LE12 5RD, UK.
Boakye, Oliver D
  • School of Biosciences, Sutton Bonington, University of Nottingham, Nottinghamshire LE12 5RD, UK.
Campeotto, Ivan
  • School of Biosciences, Sutton Bonington, University of Nottingham, Nottinghamshire LE12 5RD, UK.
Daly, Janet M
  • One Virology, School of Veterinary Medicine and Science, Sutton Bonington, University of Nottingham, Nottinghamshire LE12 5RD, UK.

MeSH Terms

  • Animals
  • African Horse Sickness / prevention & control
  • African Horse Sickness / epidemiology
  • African Horse Sickness / immunology
  • Horses
  • Viral Vaccines / immunology
  • Vaccines, Virus-Like Particle / immunology
  • Orbivirus / immunology
  • Orbivirus / genetics
  • African Horse Sickness Virus / immunology
  • Reoviridae Infections / prevention & control
  • Reoviridae Infections / veterinary
  • Reoviridae Infections / immunology
  • Plants, Genetically Modified

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 108 references
  1. Matthijnssens J., Attoui H., Bányai K., Brussaard C.P.D., Danthi P., Del Vas M., Dermody T.S., Duncan R., Fāng Q., Johne R., et al. ICTV Virus Taxonomy Profile: Sedoreoviridae 2022. J. Gen. Virol. 2022;103:001782. doi: 10.1099/jgv.0.001782.
    doi: 10.1099/jgv.0.001782pmc: PMC12643109pubmed: 36215107google scholar: lookup
  2. Theal G.M.C. Records of South-Eastern Africa: Collected in Various Libraries and Archive Departments in Europe. Government of the Cape Colony; Prieska, South Africa: 1899.
  3. Hyera J.M., Baipoledi E.K. A serological survey of African horse sickness in Botswana. J. S Afr. Vet. Assoc. 2008;79:44–45. doi: 10.4102/jsava.v79i1.240.
    doi: 10.4102/jsava.v79i1.240pubmed: 18678192google scholar: lookup
  4. Scacchia M., Molini U., Marruchella G., Maseke A., Bortone G., Cosseddu G.M., Monacoo F., Savini G., Pini A. African horse sickness outbreaks in Namibia from 2006 to 2013: Clinical, pathological and molecular findings. Vet Ital. 2015;51:123–130. doi: 10.12834/VetIt.200.617.3.
    doi: 10.12834/VetIt.200.617.3pubmed: 26129663google scholar: lookup
  5. Dennis S.J., Meyers A.E., Hitzeroth I.I., Rybicki E.P. African Horse Sickness: A Review of Current Understanding and Vaccine Development. Viruses. 2019;11:844. doi: 10.3390/v11090844.
    doi: 10.3390/v11090844pmc: PMC6783979pubmed: 31514299google scholar: lookup
  6. Barnard B.J. Epidemiology of African horse sickness and the role of the zebra in South Africa. Arch. Virol. Suppl. 1998;14:13–19. doi: 10.1007/978-3-7091-6823-3_2.
    doi: 10.1007/978-3-7091-6823-3_2pubmed: 9785491google scholar: lookup
  7. EFSA Disease Profiles: African Horse Sickness—Geographical Distribution. [(accessed on 18 May 2024)]. Available online: https://animal-diseases.efsa.europa.eu/AHSV/#Geographicaldistribution.
  8. Castillo-Olivares J. African horse sickness in Thailand: Challenges of controlling an outbreak by vaccination. Equine Vet. J. 2021;53:9–14. doi: 10.1111/evj.13353.
    doi: 10.1111/evj.13353pmc: PMC7821295pubmed: 33007121google scholar: lookup
  9. Mirchamsy H., Hazrati A. A review of the aetiology and pathology of African horse sickness. Arch. Inst. Razi. 1973;25:23–46.
  10. Assefa A., Tibebu A., Bihon A., Dagnachew A., Muktar Y. Ecological niche modeling predicting the potential distribution of African horse sickness virus from 2020 to 2060. Sci. Rep. 2022;12:1748. doi: 10.1038/s41598-022-05826-3.
    doi: 10.1038/s41598-022-05826-3pmc: PMC8811056pubmed: 35110661google scholar: lookup
  11. Wilson A.J., Mellor P.S. Bluetongue in Europe: Past, present and future. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2009;364:2669–2681. doi: 10.1098/rstb.2009.0091.
    doi: 10.1098/rstb.2009.0091pmc: PMC2865089pubmed: 19687037google scholar: lookup
  12. FAO Stock of Horses in South Africa from 2010 to 2021 (in 1000 Heads) [(accessed on 13 December 2023)]. Available online: https://www.statista.com/statistics/1306731/stock-of-horses-in-south-africa/
  13. Mdlulwa Z., Masemola M., Lubisi B.A., Chaminuka P. The financial burden of African Horse Sickness: A case of the European Union trade ban on South Africa’s horse industry. Agrekon. 2021;60:353–369. doi: 10.1080/03031853.2021.1975549.
  14. de Klerk J.N., Gorsich E.E., Grewar J.D., Atkins B.D., Tennant W.S.D., Labuschagne K., Tildesley M.J. Modelling African horse sickness emergence and transmission in the South African control area using a deterministic metapopulation approach. PLoS Comput. Biol. 2023;19:e1011448. doi: 10.1371/journal.pcbi.1011448.
  15. The European Commission Commission Implementing Regulation (EU) 2021/404. [(accessed on 2 May 2024)]. Available online: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:2021:114:FULL.
  16. Roy P., Mertens P.P., Casal I. African horse sickness virus structure. Comp. Immunol. Microbiol. Infect. Dis. 1994;17:243–273. doi: 10.1016/0147-9571(94)90046-9.
    doi: 10.1016/0147-9571(94)90046-9pubmed: 8001348google scholar: lookup
  17. Manole V., Laurinmaki P., Van Wyngaardt W., Potgieter C.A., Wright I.M., Venter G.J., van Dijk A.A., Sewell B.T., Butcher S.J. Structural insight into African horsesickness virus infection. J. Virol. 2012;86:7858–7866. doi: 10.1128/JVI.00517-12.
    doi: 10.1128/JVI.00517-12pmc: PMC3421665pubmed: 22593166google scholar: lookup
  18. Hewat E.A., Booth T.F., Roy P. Structure of bluetongue virus particles by cryoelectron microscopy. J. Struct. Biol. 1992;109:61–69. doi: 10.1016/1047-8477(92)90068-l.
    doi: 10.1016/1047-8477(92)90068-lpubmed: 1337461google scholar: lookup
  19. Iwata H., Yamagawa M., Roy P. Evolutionary relationships among the gnat-transmitted orbiviruses that cause African horse sickness, bluetongue, and epizootic hemorrhagic disease as evidenced by their capsid protein sequences. Virology. 1992;191:251–261. doi: 10.1016/0042-6822(92)90187-t.
    doi: 10.1016/0042-6822(92)90187-tpubmed: 1329319google scholar: lookup
  20. Bremer C.W., Huismans H., Van Dijk A.A. Characterization and cloning of the African horsesickness virus genome. Pt 4J. Gen. Virol. 1990;71:793–799. doi: 10.1099/0022-1317-71-4-793.
    doi: 10.1099/0022-1317-71-4-793pubmed: 2324709google scholar: lookup
  21. Zhang X., Boyce M., Bhattacharya B., Zhang X., Schein S., Roy P., Zhou Z.H. Bluetongue virus coat protein VP2 contains sialic acid-binding domains, and VP5 resembles enveloped virus fusion proteins. Proc. Natl. Acad. Sci. USA. 2010;107:6292–6297. doi: 10.1073/pnas.0913403107.
    doi: 10.1073/pnas.0913403107pmc: PMC2852009pubmed: 20332209google scholar: lookup
  22. Montiel-Garcia D., Santoyo-Rivera N., Ho P., Carrillo-Tripp M., Charles L.B., III, Johnson J.E., Reddy V.S. VIPERdb v3.0: A structure-based data analytics platform for viral capsids. Nucleic Acids Res. 2020;49:D809–D816. doi: 10.1093/nar/gkaa1096.
    doi: 10.1093/nar/gkaa1096pmc: PMC7779063pubmed: 33313778google scholar: lookup
  23. Maree S., Maree F.F., Putterill J.F., de Beer T.A.P., Huismans H., Theron J. Synthesis of empty african horse sickness virus particles. Virus Res. 2016;213:184–194. doi: 10.1016/j.virusres.2015.12.006.
  24. Uitenweerde J.M., Theron J., Stoltz M.A., Huismans H. The multimeric nonstructural NS2 proteins of bluetongue virus, African horsesickness virus, and epizootic hemorrhagic disease virus differ in their single-stranded RNA-binding ability. Virology. 1995;209:624–632. doi: 10.1006/viro.1995.1294.
    doi: 10.1006/viro.1995.1294pubmed: 7539971google scholar: lookup
  25. van de Water S.G., van Gennip R.G., Potgieter C.A., Wright I.M., van Rijn P.A. VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness Virus (AHSV) in Development of Disabled Infectious Single Animal Vaccine Candidates for AHSV. J. Virol. 2015;89:8764–8772. doi: 10.1128/JVI.01052-15.
    doi: 10.1128/JVI.01052-15pmc: PMC4524073pubmed: 26063433google scholar: lookup
  26. van Gennip R.G., van de Water S.G., van Rijn P.A. Bluetongue virus nonstructural protein NS3/NS3a is not essential for virus replication. PLoS ONE. 2014;9:e85788. doi: 10.1371/journal.pone.0085788.
  27. Boughan S., Potgieter A.C., van Staden V. African horse sickness virus NS4 is a nucleocytoplasmic protein that localizes to PML nuclear bodies. J. Gen. Virol. 2020;101:366–384. doi: 10.1099/jgv.0.001396.
    doi: 10.1099/jgv.0.001396pubmed: 32125263google scholar: lookup
  28. Boinas F., Calistrib P., Domingo M., Avilés M.M., López B.M., Sánchez B.R., Sánchez-Vizcaíno J.M. Scientific review on African Horse Sickness. EFSA Support. Publ. 2009;6:4E. doi: 10.2903/sp.efsa.2009.EN-4.
    doi: 10.2903/sp.efsa.2009.EN-4google scholar: lookup
  29. Ozawa Y., Salama S.A., Dardiri A.H. Equine Infectious Diseases: 3rd International Conference, Paris 1972. S. Karger AG; Basel, Switzerland: 1974. Methods for Recovering African Horsesickness Virus from Horse Blood1; p. 0.
  30. Clift S.J., Penrith M.L. Tissue and cell tropism of African horse sickness virus demonstrated by immunoperoxidase labeling in natural and experimental infection in horses in South Africa. Vet. Pathol. 2010;47:690–697. doi: 10.1177/0300985810370010.
    doi: 10.1177/0300985810370010pubmed: 20484177google scholar: lookup
  31. Wilson A., Mellor P.S., Szmaragd C., Mertens P.P. Adaptive strategies of African horse sickness virus to facilitate vector transmission. Vet. Res. 2009;40:16. doi: 10.1051/vetres:2008054.
    doi: 10.1051/vetres:2008054pmc: PMC2695022pubmed: 19094921google scholar: lookup
  32. Barnard B.J., Bengis R., Keet D., Dekker E.H. Epidemiology of African horsesickness: Duration of viraemia in zebra (Equus burchelli) Onderstepoort J. Vet. Res. 1994;61:391–393.
    pubmed: 7501371
  33. WOAH . Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. WOAH; Paris, France: 2023. African horse sickness (infection with African horse sickness virus)
  34. Leta S., Fetene E., Mulatu T., Amenu K., Jaleta M.B., Beyene T.J., Negussie H., Revie C.W. Modeling the global distribution of Culicoides imicola: An Ensemble approach. Sci. Rep. 2019;9:14187. doi: 10.1038/s41598-019-50765-1.
    doi: 10.1038/s41598-019-50765-1pmc: PMC6775326pubmed: 31578399google scholar: lookup
  35. Boorman J., Mellor P.S., Penn M., Jennings M. The growth of African horse-sickness virus in embryonated hen eggs and the transmission of virus by Culicoides variipennis Coquillett (Diptera, Ceratopogonidae) Arch. Virol. 1975;47:343–349. doi: 10.1007/BF01347975.
    doi: 10.1007/BF01347975pubmed: 1169930google scholar: lookup
  36. Mellor P.S., Boned J., Hamblin C., Graham S. Isolations of African horse sickness virus from vector insects made during the 1988 epizootic in Spain. Epidemiol Infect. 1990;105:447–454. doi: 10.1017/s0950268800048020.
    doi: 10.1017/s0950268800048020pmc: PMC2271884pubmed: 2209746google scholar: lookup
  37. Rodriguez M., Hooghuis H., Castano M. African horse sickness in Spain. Vet. Microbiol. 1992;33:129–142. doi: 10.1016/0378-1135(92)90041-q.
    doi: 10.1016/0378-1135(92)90041-qpubmed: 1481352google scholar: lookup
  38. Gecchele E., Merlin M., Brozzetti A., Falorni A., Pezzotti M., Avesani L. A comparative analysis of recombinant protein expression in different biofactories: Bacteria, insect cells and plant systems. J. Vis. Exp. 2015:52459. doi: 10.3791/52459.
    doi: 10.3791/52459pmc: PMC4401374pubmed: 25867956google scholar: lookup
  39. Carpenter S., Mellor P.S., Fall A.G., Garros C., Venter G.J. African Horse Sickness Virus: History, Transmission, and Current Status. Annu. Rev. Entomol. 2017;62:343–358. doi: 10.1146/annurev-ento-031616-035010.
  40. von Teichman B.F., Dungu B., Smit T.K. In vivo cross-protection to African horse sickness Serotypes 5 and 9 after vaccination with Serotypes 8 and 6. Vaccine. 2010;28:6505–6517. doi: 10.1016/j.vaccine.2010.06.105.
    doi: 10.1016/j.vaccine.2010.06.105pubmed: 20638456google scholar: lookup
  41. Hanley K.A. The double-edged sword: How evolution can make or break a live-attenuated virus vaccine. Evolution. 2011;4:635–643. doi: 10.1007/s12052-011-0365-y.
    doi: 10.1007/s12052-011-0365-ypmc: PMC3314307pubmed: 22468165google scholar: lookup
  42. Weyer C.T., Grewar J.D., Burger P., Rossouw E., Lourens C., Joone C., le Grange M., Coetzee P., Venter E., Martin D.P., et al. African Horse Sickness Caused by Genome Reassortment and Reversion to Virulence of Live, Attenuated Vaccine Viruses, South Africa, 2004–2014. Emerg Infect Dis. 2016;22:2087–2096. doi: 10.3201/eid2212.160718.
    doi: 10.3201/eid2212.160718pmc: PMC5189153pubmed: 27442883google scholar: lookup
  43. Paweska J.T., Prinsloo S., Venter G.J. Oral susceptibility of South African Culicoides species to live-attenuated serotype-specific vaccine strains of African horse sickness virus (AHSV) Med. Vet. Entomol. 2003;17:436–447. doi: 10.1111/j.1365-2915.2003.00467.x.
  44. Lee Y.T., Ko E.J., Lee Y., Kim K.H., Kim M.C., Lee Y.N., Kang S.M. Intranasal vaccination with M2e5x virus-like particles induces humoral and cellular immune responses conferring cross-protection against heterosubtypic influenza viruses. PLoS ONE. 2018;13:e0190868. doi: 10.1371/journal.pone.0190868.
  45. Wang C., Zheng X., Gai W., Wong G., Wang H., Jin H., Feng N., Zhao Y., Zhang W., Li N., et al. Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice. Antivir. Res. 2017;140:55–61. doi: 10.1016/j.antiviral.2016.12.019.
  46. de Oliveira C.M., Fregnani J., Villa L.L. HPV Vaccine: Updates and Highlights. Acta Cytol. 2019;63:159–168. doi: 10.1159/000497617.
    doi: 10.1159/000497617pubmed: 30870844google scholar: lookup
  47. Kheirvari M., Liu H., Tumban E. Virus-like Particle Vaccines and Platforms for Vaccine Development. Viruses. 2023;15:1109. doi: 10.3390/v15051109.
    doi: 10.3390/v15051109pmc: PMC10223759pubmed: 37243195google scholar: lookup
  48. Pushko P., Tretyakova I., Hidajat R., Zsak A., Chrzastek K., Tumpey T.M., Kapczynski D.R. Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens. Virology. 2017;501:176–182. doi: 10.1016/j.virol.2016.12.001.
    doi: 10.1016/j.virol.2016.12.001pmc: PMC5266608pubmed: 27936463google scholar: lookup
  49. Smith T., O’Kennedy M.M., Wandrag D.B.R., Adeyemi M., Abolnik C. Efficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza A H6N2 virus. Plant Biotechnol. J. 2020;18:502–512. doi: 10.1111/pbi.13219.
    doi: 10.1111/pbi.13219pmc: PMC6953208pubmed: 31350931google scholar: lookup
  50. Matsuo E., Celma C.C., Roy P. A reverse genetics system of African horse sickness virus reveals existence of primary replication. FEBS Lett. 2010;584:3386–3391. doi: 10.1016/j.febslet.2010.06.030.
    doi: 10.1016/j.febslet.2010.06.030pubmed: 20600010google scholar: lookup
  51. Brune K.D., Leneghan D.B., Brian I.J., Ishizuka A.S., Bachmann M.F., Draper S.J., Biswas S., Howarth M. Plug-and-Display: Decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Sci. Rep. 2016;6:19234. doi: 10.1038/srep19234.
    doi: 10.1038/srep19234pmc: PMC4725971pubmed: 26781591google scholar: lookup
  52. Terao Y., Kawabata S., Nakata M., Nakagawa I., Hamada S. Molecular characterization of a novel fibronectin-binding protein of Streptococcus pyogenes strains isolated from toxic shock-like syndrome patients. J. Biol. Chem. 2002;277:47428–47435. doi: 10.1074/jbc.M209133200.
    doi: 10.1074/jbc.M209133200pubmed: 12359713google scholar: lookup
  53. Zakeri B., Fierer J.O., Celik E., Chittock E.C., Schwarz-Linek U., Moy V.T., Howarth M. Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin. Proc. Natl. Acad. Sci. USA. 2012;109:E690–E697. doi: 10.1073/pnas.1115485109.
    doi: 10.1073/pnas.1115485109pmc: PMC3311370pubmed: 22366317google scholar: lookup
  54. Marini A., Zhou Y., Li Y., Taylor I.J., Leneghan D.B., Jin J., Zaric M., Mekhaiel D., Long C.A., Miura K., et al. A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response. Front. Immunol. 2019;10:2931. doi: 10.3389/fimmu.2019.02931.
    doi: 10.3389/fimmu.2019.02931pmc: PMC6921968pubmed: 31921185google scholar: lookup
  55. Rahikainen R., Rijal P., Tan T.K., Wu H.J., Andersson A.C., Barrett J.R., Bowden T.A., Draper S.J., Townsend A.R., Howarth M. Overcoming Symmetry Mismatch in Vaccine Nanoassembly through Spontaneous Amidation. Angew. Chem. Int. Ed. Engl. 2021;60:321–330. doi: 10.1002/anie.202009663.
    doi: 10.1002/anie.202009663pmc: PMC7821241pubmed: 32886840google scholar: lookup
  56. Sheng Y., Li Z., Lin X., Ma Y., Ren Y., Su Z., Ma G., Zhang S. The position of Spy Tag/Catcher system in hepatitis B core protein particles affects the immunogenicity and stability of the synthetic vaccine. Vaccine. 2023;41:4867–4878. doi: 10.1016/j.vaccine.2023.06.070.
    doi: 10.1016/j.vaccine.2023.06.070pubmed: 37391312google scholar: lookup
  57. Sungwa M., Susan T., Mikkel J.C., Adolph K.R., Boniface M.S., Grundtvig T.T., Ali S., Agertoug N.M., Frederik S.A. A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses. Afr. Health Sci. 2017;17:373–381. doi: 10.4314/ahs.v17i2.11.
    doi: 10.4314/ahs.v17i2.11pmc: PMC5637022pubmed: 29062332google scholar: lookup
  58. Tan T.K., Rijal P., Rahikainen R., Keeble A.H., Schimanski L., Hussain S., Harvey R., Hayes J.W.P., Edwards J.C., McLean R.K., et al. A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses. Nat. Commun. 2021;12:542. doi: 10.1038/s41467-020-20654-7.
    doi: 10.1038/s41467-020-20654-7pmc: PMC7822889pubmed: 33483491google scholar: lookup
  59. Gupta R., Arora K., Roy S.S., Joseph A., Rastogi R., Arora N.M., Kundu P.K. Platforms, advances, and technical challenges in virus-like particles-based vaccines. Front. Immunol. 2023;14:1123805. doi: 10.3389/fimmu.2023.1123805.
    doi: 10.3389/fimmu.2023.1123805pmc: PMC9947793pubmed: 36845125google scholar: lookup
  60. Mohsen M.O., Zha L., Cabral-Miranda G., Bachmann M.F. Major findings and recent advances in virus-like particle (VLP)-based vaccines. Semin. Immunol. 2017;34:123–132. doi: 10.1016/j.smim.2017.08.014.
    doi: 10.1016/j.smim.2017.08.014pubmed: 28887001google scholar: lookup
  61. Roldao A., Mellado M.C., Castilho L.R., Carrondo M.J., Alves P.M. Virus-like particles in vaccine development. Expert. Rev. Vaccines. 2010;9:1149–1176. doi: 10.1586/erv.10.115.
    doi: 10.1586/erv.10.115pubmed: 20923267google scholar: lookup
  62. Ojha R., Prajapati V.K. Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity. J. Cell Physiol. 2021;236:8020–8034. doi: 10.1002/jcp.30483.
    doi: 10.1002/jcp.30483pmc: PMC8427110pubmed: 34170014google scholar: lookup
  63. Scheiblhofer S., Laimer J., Machado Y., Weiss R., Thalhamer J. Influence of protein fold stability on immunogenicity and its implications for vaccine design. Expert. Rev. Vaccines. 2017;16:479–489. doi: 10.1080/14760584.2017.1306441.
  64. Moradi Vahdat M., Hemmati F., Ghorbani A., Rutkowska D., Afsharifar A., Eskandari M.H., Rezaei N., Niazi A. Hepatitis B core-based virus-like particles: A platform for vaccine development in plants. Biotechnol. Rep. 2021;29:e00605. doi: 10.1016/j.btre.2021.e00605.
    doi: 10.1016/j.btre.2021.e00605pmc: PMC7937989pubmed: 33732633google scholar: lookup
  65. Sahdev S., Khattar S.K., Saini K.S. Production of active eukaryotic proteins through bacterial expression systems: A review of the existing biotechnology strategies. Mol. Cell Biochem. 2008;307:249–264. doi: 10.1007/s11010-007-9603-6.
    doi: 10.1007/s11010-007-9603-6pubmed: 17874175google scholar: lookup
  66. Hassine I.H., M’hadheb M.B., Almalki M.A., Gharbi J. Virus-like particles as powerful vaccination strategy against human viruses. Rev. Med. Virol. 2024;34:e2498. doi: 10.1002/rmv.2498.
    doi: 10.1002/rmv.2498pubmed: 38116958google scholar: lookup
  67. Chang J.C., Lee S.J., Kim J.S., Wang C.H., Nai Y.S. Transient Expression of Foreign Genes in Insect Cells (sf9) for Protein Functional Assay. J. Vis. Exp. 2018:56693. doi: 10.3791/56693.
    doi: 10.3791/56693pmc: PMC5931320pubmed: 29553499google scholar: lookup
  68. Hong M., Li T., Xue W., Zhang S., Cui L., Wang H., Zhang Y., Zhou L., Gu Y., Xia N., et al. Genetic engineering of baculovirus-insect cell system to improve protein production. Front. Bioeng. Biotechnol. 2022;10:994743. doi: 10.3389/fbioe.2022.994743.
    doi: 10.3389/fbioe.2022.994743pmc: PMC9530357pubmed: 36204465google scholar: lookup
  69. Burnett M.J.B., Burnett A.C. Therapeutic recombinant protein production in plants: Challenges and opportunities. Plants People Planet. 2020;2:121–132. doi: 10.1002/ppp3.10073.
    doi: 10.1002/ppp3.10073google scholar: lookup
  70. Fischer R., Buyel J.F. Molecular farming—The slope of enlightenment. Biotechnol. Adv. 2020;40:107519. doi: 10.1016/j.biotechadv.2020.107519.
  71. Schillberg S., Raven N., Spiegel H., Rasche S., Buntru M. Critical analysis of the commercial potential of plants for the production of recombinant proteins. Front. Plant Sci. 2019;10:720. doi: 10.3389/fpls.2019.00720.
    doi: 10.3389/fpls.2019.00720pmc: PMC6579924pubmed: 31244868google scholar: lookup
  72. Buntru M., Hahnengress N., Croon A., Schillberg S. Plant-Derived Cell-Free Biofactories for the Production of Secondary Metabolites. Front. Plant Sci. 2021;12:794999. doi: 10.3389/fpls.2021.794999.
    doi: 10.3389/fpls.2021.794999pmc: PMC8832058pubmed: 35154185google scholar: lookup
  73. Huang T.-K., McDonald K.A. Bioreactor engineering for recombinant protein production in plant cell suspension cultures. Biochem. Eng. J. 2009;45:168–184. doi: 10.1016/j.bej.2009.02.008.
    doi: 10.1016/j.bej.2009.02.008google scholar: lookup
  74. Karki U., Fang H., Guo W., Unnold-Cofre C., Xu J. Cellular engineering of plant cells for improved therapeutic protein production. Plant Cell Rep. 2021;40:1087–1099. doi: 10.1007/s00299-021-02693-6.
    doi: 10.1007/s00299-021-02693-6pmc: PMC8035600pubmed: 33837823google scholar: lookup
  75. Sainsbury F., Thuenemann E.C., Lomonossoff G.P. pEAQ: Versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol. J. 2009;7:682–693. doi: 10.1111/j.1467-7652.2009.00434.x.
  76. Mason H.S., Lam D.M., Arntzen C.J. Expression of hepatitis B surface antigen in transgenic plants. Proc. Natl. Acad. Sci. USA. 1992;89:11745–11749. doi: 10.1073/pnas.89.24.11745.
    doi: 10.1073/pnas.89.24.11745pmc: PMC50633pubmed: 1465391google scholar: lookup
  77. Gunter C.J., Regnard G.L., Rybicki E.P., Hitzeroth I.I. Immunogenicity of plant-produced porcine circovirus-like particles in mice. Plant Biotechnol. J. 2019;17:1751–1759. doi: 10.1111/pbi.13097.
    doi: 10.1111/pbi.13097pmc: PMC6686138pubmed: 30791210google scholar: lookup
  78. D’Aoust M.A., Couture M.M., Charland N., Trepanier S., Landry N., Ors F., Vezina L.P. The production of hemagglutinin-based virus-like particles in plants: A rapid, efficient and safe response to pandemic influenza. Plant Biotechnol. J. 2010;8:607–619. doi: 10.1111/j.1467-7652.2009.00496.x.
  79. Pillet S., Racine T., Nfon C., Di Lenardo T.Z., Babiuk S., Ward B.J., Kobinger G.P., Landry N. Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets. Vaccine. 2015;33:6282–6289. doi: 10.1016/j.vaccine.2015.09.065.
    doi: 10.1016/j.vaccine.2015.09.065pubmed: 26432915google scholar: lookup
  80. Marillonnet S., Giritch A., Gils M., Kandzia R., Klimyuk V., Gleba Y. In planta engineering of viral RNA replicons: Efficient assembly by recombination of DNA modules delivered by Agrobacterium. Proc. Natl. Acad. Sci. USA. 2004;101:6852–6857. doi: 10.1073/pnas.0400149101.
    doi: 10.1073/pnas.0400149101pmc: PMC406431pubmed: 15103020google scholar: lookup
  81. Leroux-Roels I., Maes C., Joye J., Jacobs B., Jarczowski F., Diessner A., Janssens Y., Waerlop G., Tamminen K., Heinimäki S., et al. A randomized, double-blind, placebo-controlled, dose-escalating phase I trial to evaluate safety and immunogenicity of a plant-produced, bivalent, recombinant norovirus-like particle vaccine. Front. Immunol. 2022;13:1021500. doi: 10.3389/fimmu.2022.1021500.
    doi: 10.3389/fimmu.2022.1021500pmc: PMC9585308pubmed: 36275772google scholar: lookup
  82. Peyret H., Brown J.K.M., Lomonossoff G.P. Improving plant transient expression through the rational design of synthetic 5’ and 3’ untranslated regions. Plant Methods. 2019;15:108. doi: 10.1186/s13007-019-0494-9.
    doi: 10.1186/s13007-019-0494-9pmc: PMC6749642pubmed: 31548848google scholar: lookup
  83. van Rijn P.A. Prospects of Next-Generation Vaccines for Bluetongue. Front. Vet. Sci. 2019;6:407. doi: 10.3389/fvets.2019.00407.
    doi: 10.3389/fvets.2019.00407pmc: PMC6881303pubmed: 31824966google scholar: lookup
  84. Thuenemann E.C., Meyers A.E., Verwey J., Rybicki E.P., Lomonossoff G.P. A method for rapid production of heteromultimeric protein complexes in plants: Assembly of protective bluetongue virus-like particles. Plant Biotechnol. J. 2013;11:839–846. doi: 10.1111/pbi.12076.
    doi: 10.1111/pbi.12076pubmed: 23647743google scholar: lookup
  85. Gwynn A., Mbewana S., Lubisi B.A., Tshabalala H.M., Rybicki E.P., Meyers A.E. Chimaeric plant-produced bluetongue virus particles as potential vaccine candidates. Arch. Virol. 2023;168:179. doi: 10.1007/s00705-023-05790-x.
    doi: 10.1007/s00705-023-05790-xpmc: PMC10264491pubmed: 37310539google scholar: lookup
  86. Mokoena N.B., Moetlhoa B., Rutkowska D.A., Mamputha S., Dibakwane V.S., Tsekoa T.L., O’Kennedy M.M. Plant-produced Bluetongue chimaeric VLP vaccine candidates elicit serotype-specific immunity in sheep. Vaccine. 2019;37:6068–6075. doi: 10.1016/j.vaccine.2019.08.042.
    doi: 10.1016/j.vaccine.2019.08.042pubmed: 31471154google scholar: lookup
  87. Dennis S.J., Meyers A.E., Guthrie A.J., Hitzeroth I.I., Rybicki E.P. Immunogenicity of plant-produced African horse sickness virus-like particles: Implications for a novel vaccine. Plant Biotechnol. J. 2018;16:442–450. doi: 10.1111/pbi.12783.
    doi: 10.1111/pbi.12783pmc: PMC5787833pubmed: 28650085google scholar: lookup
  88. Dennis S.J., O’Kennedy M.M., Rutkowska D., Tsekoa T., Lourens C.W., Hitzeroth I.I., Meyers A.E., Rybicki E.P. Safety and immunogenicity of plant-produced African horse sickness virus-like particles in horses. Vet. Res. 2018;49:105. doi: 10.1186/s13567-018-0600-4.
    doi: 10.1186/s13567-018-0600-4pmc: PMC6389048pubmed: 30309390google scholar: lookup
  89. Rutkowska D.A., Mokoena N.B., Tsekoa T.L., Dibakwane V.S., O’Kennedy M.M. Plant-produced chimeric virus-like particles—A new generation vaccine against African horse sickness. BMC Vet. Res. 2019;15:432. doi: 10.1186/s12917-019-2184-2.
    doi: 10.1186/s12917-019-2184-2pmc: PMC6892175pubmed: 31796116google scholar: lookup
  90. O’Kennedy M.M., Coetzee P., Koekemoer O., du Plessis L., Lourens C.W., Kwezi L., du Preez I., Mamputha S., Mokoena N.B., Rutkowska D.A., et al. Protective immunity of plant-produced African horse sickness virus serotype 5 chimaeric virus-like particles (VLPs) and viral protein 2 (VP2) vaccines in IFNAR(-/-) mice. Vaccine. 2022;40:5160–5169. doi: 10.1016/j.vaccine.2022.06.079.
    doi: 10.1016/j.vaccine.2022.06.079pubmed: 35902279google scholar: lookup
  91. O’Kennedy M.M., Roth R., Ebersohn K., du Plessis L.H., Mamputha S., Rutkowska D.A., du Preez I., Verschoor J.A., Lemmer Y. Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice. PLoS ONE. 2024;19:e0301340. doi: 10.1371/journal.pone.0301340.
  92. Nandi S., Kwong A.T., Holtz B.R., Erwin R.L., Marcel S., McDonald K.A. Techno-economic analysis of a transient plant-based platform for monoclonal antibody production. mAbs. 2016;8:1456–1466. doi: 10.1080/19420862.2016.1227901.
  93. Tusé D., Tu T., McDonald K.A. Manufacturing Economics of Plant-Made Biologics: Case Studies in Therapeutic and Industrial Enzymes. BioMed Res. Int. 2014;2014:256135. doi: 10.1155/2014/256135.
    doi: 10.1155/2014/256135pmc: PMC4058100pubmed: 24977145google scholar: lookup
  94. Feng Z., Li X., Fan B., Zhu C., Chen Z. Maximizing the Production of Recombinant Proteins in Plants: From Transcription to Protein Stability. Int. J. Mol. Sci. 2022;23:13516. doi: 10.3390/ijms232113516.
    doi: 10.3390/ijms232113516pmc: PMC9659199pubmed: 36362299google scholar: lookup
  95. Jansing J., Bortesi L. Knockout of Glycosyltransferases in Nicotiana benthamianaNicotianabenthamianaby Genome EditingGenome editing to Improve GlycosylationGlycosylationGenome editingNicotianabenthamianaof Plant-Produced Proteins. In: Schillberg S., Spiegel H., editors. Recombinant Proteins in Plants: Methods and Protocols. Springer; New York, NY, USA: 2022. pp. 241–284.
  96. Norkunas K., Harding R., Dale J., Dugdale B. Improving agroinfiltration-based transient gene expression in Nicotiana benthamiana. Plant Methods. 2018;14:71. doi: 10.1186/s13007-018-0343-2.
    doi: 10.1186/s13007-018-0343-2pmc: PMC6109318pubmed: 30159002google scholar: lookup
  97. Buyel J.F. Strategies for Efficient and Sustainable Protein ExtractionProteinextractionsand PurificationPurificationProteinextractionsfrom Plant Tissues. In: Schillberg S., Spiegel H., editors. Recombinant Proteins in Plants: Methods and Protocols. Springer; New York, NY, USA: 2022. pp. 127–145.
  98. Kahl L., Molloy J., Patron N., Matthewman C., Haseloff J., Grewal D., Johnson R., Endy D. Opening options for material transfer. Nat. Biotechnol. 2018;36:923–927. doi: 10.1038/nbt.4263.
    doi: 10.1038/nbt.4263pmc: PMC6871013pubmed: 30307930google scholar: lookup
  99. 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:e5997. doi: 10.1371/journal.pone.0005997.
  100. 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;32:3670–3674. doi: 10.1016/j.vaccine.2014.04.036.
  101. Castillo-Olivares J., Calvo-Pinilla E., Casanova I., Bachanek-Bankowska K., Chiam R., Maan S., Nieto J.M., Ortego J., Mertens P.P.C. 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:e16503. doi: 10.1371/journal.pone.0016503.
  102. Calvo-Pinilla E., de la Poza F., Gubbins S., Mertens P.P.C., 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. doi: 10.1016/j.virusres.2013.12.002.
  103. de la Poza F., Calvo-Pinilla E., López-Gil E., Marín-López 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. doi: 10.1371/journal.pone.0070197.
  104. Faqih L., Vallely P., Klapper P. Genetic stability of SIV Gag/Tat gene inserted into Del-II in modified vaccinia virus ankara after serial passage of recombinant vector in pCEFs cells. J. Virol. Methods. 2023;312:114651. doi: 10.1016/j.jviromet.2022.114651.
  105. Neckermann P., Mohr M., Billmeier M., Karlas A., Boilesen D.R., Thirion C., Holst P.J., Jordan I., Sandig V., Asbach B., et al. Transgene expression knock-down in recombinant Modified Vaccinia virus Ankara vectors improves genetic stability and sustained transgene maintenance across multiple passages. Front. Immunol. 2024;15:1338492. doi: 10.3389/fimmu.2024.1338492.
    doi: 10.3389/fimmu.2024.1338492pmc: PMC10877035pubmed: 38380318google scholar: lookup
  106. van Rijn P.A., Maris-Veldhuis M.A., Potgieter C.A., van Gennip R.G.P. African horse sickness virus (AHSV) with a deletion of 77 amino acids in NS3/NS3a protein is not virulent and a safe promising AHS Disabled Infectious Single Animal (DISA) vaccine platform. Vaccine. 2018;36:1925–1933. doi: 10.1016/j.vaccine.2018.03.003.
    doi: 10.1016/j.vaccine.2018.03.003pubmed: 29525278google scholar: lookup
  107. Lulla V., Losada A., Lecollinet S., Kerviel A., Lilin T., Sailleau C., Beck C., Zientara S., Roy P. Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge. Vaccine. 2017;35:4262–4269. doi: 10.1016/j.vaccine.2017.06.023.
  108. Attoui H., Mendez-Lopez M.R., Rao S., Hurtado-Alendes A., Lizaraso-Caparo F., Mohd Jaafar F., Samuel A.R., Belhouchet M., Pritchard L.I., Melville L., et al. Peruvian horse sickness virus and Yunnan orbivirus, isolated from vertebrates and mosquitoes in Peru and Australia. Virology. 2009;394:298–310. doi: 10.1016/j.virol.2009.08.032.
    doi: 10.1016/j.virol.2009.08.032pubmed: 19766284google scholar: lookup

Citations

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  1. Peralta-Cuevas E, Garcia-Atutxa I, Huerta-Saquero A, Villanueva-Flores F. The Role of Plant Virus-like Particles in Advanced Drug Delivery and Vaccine Development: Structural Attributes and Application Potential.. Viruses 2025 Jan 23;17(2).
    doi: 10.3390/v17020148pubmed: 40006903google scholar: lookup