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Home / Equine Research Bank / Vaccine / A recombinant envelope protein vaccine against West Nile vir...
Vaccine2005; 23(30); 3915-3924; doi: 10.1016/j.vaccine.2005.03.006

A recombinant envelope protein vaccine against West Nile virus.

Abstract: West Nile (WN) virus is a flavivirus that first appeared in North America in 1999. Since then, more than 600 human deaths and 22,000 equine infections have been attributed to the virus in the United States. We expressed a truncated form of WN virus envelope (E) protein in Drosophila S2 cells. This soluble recombinant E protein was recognized by antibodies from naturally infected horses, indicating that it contains native epitopes. Mice and horses produced high-titer antibodies when immunized with recombinant E protein combined with aluminum hydroxide. Immunized mice were resistant to challenge with a lethal viral dose. Sera from immunized horses, administered to naive mice, conferred resistance against a lethal WN viral challenge. In addition, sera of immunized horses neutralized West Nile virus in vitro, as demonstrated by plaque reduction assays. This recombinant form of E protein, combined with aluminum hydroxide, is a candidate vaccine that may protect humans and horses against WN virus infections.
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Publication Date: 2005-04-06 PubMed ID: 15917113DOI: 10.1016/j.vaccine.2005.03.006Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • U.S. Gov't
  • P.H.S.

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 investigates a vaccine against West Nile Virus, developed from a recombinant envelope protein of the virus, which when combined with aluminum hydroxide shows strong antibody responses in mice and horses and offers protection against lethal doses of the virus.

Objective of the Research

The study aims at developing a vaccine against West Nile Virus using a recombinant version of the West Nile Virus envelope protein, expressed in Drosophila S2 cells. The objective is to prove the efficacy of the vaccine in producing high-titer antibodies and providing resistance against lethal doses of the virus.

Methods and Procedure of Research

  • The researchers express a truncated form of WN virus envelope (E) protein in Drosophila S2 cells to create a soluble, recombinant E protein.
  • An initial analysis indicates that this recombinant protein contains native epitopes, as it is recognized by antibodies from naturally infected horses.
  • The researchers then proceed to immunize mice and horses with recombinant E protein combined with aluminum hydroxide to determine if this would stimulate the production of high-titer antibodies.
  • The immunized mice are subjected to a lethal dose of the WN virus to determine if the vaccine confers resistance.
  • Furthermore, sera derived from the immunized horses were administered to naive mice to test if this could confer resistance against a lethal WN viral challenge.

Results of Research

  • The results started to confirm that mice and horses immunized with the vaccine produced high-titer antibodies, proving the vaccine effective in stimulating an immune response.
  • Immunized mice demonstrated resistance when challenged with a lethal dose of the virus, implying the vaccine’s potential in preventing infection.
  • Similarly, the sera from immunized horses conferred resistance to naive mice exposed to lethal doses of the WN virus, thus evidencing the protective capabilities of vaccine-induced antibodies.
  • The sera from immunized horses also demonstrated the capability to neutralize the virus in vitro.

Conclusion

The research concludes that the recombinant E protein, combined with aluminum hydroxide, can be an effective vaccine against the West Nile Virus for horses and potentially humans. This vaccine creates a strong immune response and can protect against lethal exposures to the virus, hence becoming a promising candidate for countering WN virus infections.

Cite This Article

APA
Ledizet M, Kar K, Foellmer HG, Wang T, Bushmich SL, Anderson JF, Fikrig E, Koski RA. (2005). A recombinant envelope protein vaccine against West Nile virus. Vaccine, 23(30), 3915-3924. https://doi.org/10.1016/j.vaccine.2005.03.006

Publication

Vaccine
ISSN: 0264-410X
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 23
Issue: 30
Pages: 3915-3924

Researcher Affiliations

Ledizet, Michel
  • L2 Diagnostics, LLC, 300 George Street, New Haven, CT 06511, USA. michel.ledizet@L2dx.com
Kar, Kalipada
    Foellmer, Harald G
      Wang, Tian
        Bushmich, Sandra L
          Anderson, John F
            Fikrig, Erol
              Koski, Raymond A

                MeSH Terms

                • Adjuvants, Immunologic
                • Aluminum Hydroxide / pharmacology
                • Animals
                • Cells, Cultured
                • Drosophila
                • Female
                • Horses
                • Immunization, Passive
                • Immunoglobulin G / biosynthesis
                • Immunoglobulin G / genetics
                • Male
                • Mice
                • Mice, Inbred C57BL
                • Protein Conformation
                • Vaccines, Synthetic / immunology
                • Viral Envelope Proteins / genetics
                • Viral Envelope Proteins / immunology
                • Viral Plaque Assay
                • Viral Vaccines / immunology
                • West Nile Fever / prevention & control
                • West Nile virus / immunology

                Grant Funding

                • AI49646 / NIAID NIH HHS

                Citations

                This article has been cited 34 times.
                1. Mertinková P, Mochnáčová E, Bhide K, Kulkarni A, Tkáčová Z, Hruškovicová J, Bhide M. Development of peptides targeting receptor binding site of the envelope glycoprotein to contain the West Nile virus infection.. Sci Rep 2021 Oct 11;11(1):20131.
                  doi: 10.1038/s41598-021-99696-wpubmed: 34635758google scholar: lookup
                2. Araujo SC, Pereira LR, Alves RPS, Andreata-Santos R, Kanno AI, Ferreira LCS, Gonçalves VM. Anti-Flavivirus Vaccines: Review of the Present Situation and Perspectives of Subunit Vaccines Produced in Escherichia coli.. Vaccines (Basel) 2020 Aug 31;8(3).
                  doi: 10.3390/vaccines8030492pubmed: 32878023google scholar: lookup
                3. Mertinková P, Kulkarni A, Káňová E, Bhide K, Tkáčová Z, Bhide M. A simple and rapid pipeline for identification of receptor-binding sites on the surface proteins of pathogens.. Sci Rep 2020 Jan 24;10(1):1163.
                  doi: 10.1038/s41598-020-58305-ypubmed: 31980725google scholar: lookup
                4. Acharya D, Bai F. An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection.. Methods Mol Biol 2016;1435:249-91.
                  doi: 10.1007/978-1-4939-3670-0_19pubmed: 27188563google scholar: lookup
                5. Van Hoeven N, Joshi SW, Nana GI, Bosco-Lauth A, Fox C, Bowen RA, Clements DE, Martyak T, Parks DE, Baldwin S, Reed SG, Coler RN. A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations.. PLoS One 2016;11(2):e0149610.
                  doi: 10.1371/journal.pone.0149610pubmed: 26901122google scholar: lookup
                6. Tinker JK, Yan J, Knippel RJ, Panayiotou P, Cornell KA. Immunogenicity of a West Nile virus DIII-cholera toxin A2/B chimera after intranasal delivery.. Toxins (Basel) 2014 Apr 22;6(4):1397-418.
                  doi: 10.3390/toxins6041397pubmed: 24759174google scholar: lookup
                7. Amanna IJ, Slifka MK. Current trends in West Nile virus vaccine development.. Expert Rev Vaccines 2014 May;13(5):589-608.
                  doi: 10.1586/14760584.2014.906309pubmed: 24689659google scholar: lookup
                8. Nzonza A, Lecollinet S, Chat S, Lowenski S, Mérour E, Biacchesi S, Brémont M. A recombinant novirhabdovirus presenting at the surface the E Glycoprotein from West Nile Virus (WNV) is immunogenic and provides partial protection against lethal WNV challenge in BALB/c mice.. PLoS One 2014;9(3):e91766.
                  doi: 10.1371/journal.pone.0091766pubmed: 24663075google scholar: lookup
                9. Austin SK, Dowd KA. B cell response and mechanisms of antibody protection to West Nile virus.. Viruses 2014 Mar 3;6(3):1015-36.
                  doi: 10.3390/v6031015pubmed: 24594676google scholar: lookup
                10. Marka A, Diamantidis A, Papa A, Valiakos G, Chaintoutis SC, Doukas D, Tserkezou P, Giannakopoulos A, Papaspyropoulos K, Patsoula E, Badieritakis E, Baka A, Tseroni M, Pervanidou D, Papadopoulos NT, Koliopoulos G, Tontis D, Dovas CI, Billinis C, Tsakris A, Kremastinou J, Hadjichristodoulou C, Vakalis N, Vassalou E, Zarzani S, Zounos A, Komata K, Balatsos G, Beleri S, Mpimpa A, Papavasilopoulos V, Rodis I, Spanakos G, Tegos N, Spyrou V, Dalabiras Z, Birtsas P, Athanasiou L, Papanastassopoulou M, Ioannou C, Athanasiou C, Gerofotis C, Papadopoulou E, Testa T, Tsakalidou O, Rachiotis G, Bitsolas N, Mamouris Z, Moutou K, Sarafidou T, Stamatis K, Sarri K, Tsiodras S, Georgakopoulou T, Detsis M, Mavrouli M, Stavropoulou A, Politi L, Mageira G, Christopoulou V, Diamantopoulou G, Spanakis N, Vrioni G, Piperaki ET, Mitsopoulou K, Kioulos I, Michaelakis A, Stathis I, Tselentis I, Psaroulaki A, Keramarou M, Chochlakis D, Photis Y, Konstantinou M, Manetos P, Tsobanoglou S, Mourelatos S, Antalis V, Pergantas P, Eleftheriou G. West Nile virus state of the art report of MALWEST Project.. Int J Environ Res Public Health 2013 Dec 2;10(12):6534-610.
                  doi: 10.3390/ijerph10126534pubmed: 24317379google scholar: lookup
                11. Brandler S, Tangy F. Vaccines in development against West Nile virus.. Viruses 2013 Sep 30;5(10):2384-409.
                  doi: 10.3390/v5102384pubmed: 24084235google scholar: lookup
                12. Iyer AV, Kousoulas KG. A review of vaccine approaches for West Nile virus.. Int J Environ Res Public Health 2013 Sep 10;10(9):4200-23.
                  doi: 10.3390/ijerph10094200pubmed: 24025396google scholar: lookup
                13. Xie G, Welte T, Wang J, Whiteman MC, Wicker JA, Saxena V, Cong Y, Barrett AD, Wang T. A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways.. Vaccine 2013 Aug 28;31(38):4143-51.
                  doi: 10.1016/j.vaccine.2013.06.093pubmed: 23845800google scholar: lookup
                14. Namekar M, Kumar M, O'Connell M, Nerurkar VR. Effect of serum heat-inactivation and dilution on detection of anti-WNV antibodies in mice by West Nile virus E-protein microsphere immunoassay.. PLoS One 2012;7(9):e45851.
                  doi: 10.1371/journal.pone.0045851pubmed: 23049879google scholar: lookup
                15. Biswas S, Chang H, Sarkis PT, Fikrig E, Zhu Q, Marasco WA. Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5+ B cells.. Immunology 2011 Dec;134(4):419-33.
                  doi: 10.1111/j.1365-2567.2011.03501.xpubmed: 22044090google scholar: lookup
                16. Biedenbender R, Bevilacqua J, Gregg AM, Watson M, Dayan G. Phase II, randomized, double-blind, placebo-controlled, multicenter study to investigate the immunogenicity and safety of a West Nile virus vaccine in healthy adults.. J Infect Dis 2011 Jan 1;203(1):75-84.
                  doi: 10.1093/infdis/jiq003pubmed: 21148499google scholar: lookup
                17. Lawson CL, Baker ML, Best C, Bi C, Dougherty M, Feng P, van Ginkel G, Devkota B, Lagerstedt I, Ludtke SJ, Newman RH, Oldfield TJ, Rees I, Sahni G, Sala R, Velankar S, Warren J, Westbrook JD, Henrick K, Kleywegt GJ, Berman HM, Chiu W. EMDataBank.org: unified data resource for CryoEM.. Nucleic Acids Res 2011 Jan;39(Database issue):D456-64.
                  doi: 10.1093/nar/gkq880pubmed: 20935055google scholar: lookup
                18. Lawson CL. Unified data resource for cryo-EM.. Methods Enzymol 2010;483:73-90.
                  doi: 10.1016/S0076-6879(10)83004-6pubmed: 20888470google scholar: lookup
                19. Kuwahara M, Konishi E. Evaluation of extracellular subviral particles of dengue virus type 2 and Japanese encephalitis virus produced by Spodoptera frugiperda cells for use as vaccine and diagnostic antigens.. Clin Vaccine Immunol 2010 Oct;17(10):1560-6.
                  doi: 10.1128/CVI.00087-10pubmed: 20668137google scholar: lookup
                20. Demento SL, Bonafé N, Cui W, Kaech SM, Caplan MJ, Fikrig E, Ledizet M, Fahmy TM. TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitis.. J Immunol 2010 Sep 1;185(5):2989-97.
                  doi: 10.4049/jimmunol.1000768pubmed: 20660705google scholar: lookup
                21. Spohn G, Jennings GT, Martina BE, Keller I, Beck M, Pumpens P, Osterhaus AD, Bachmann MF. A VLP-based vaccine targeting domain III of the West Nile virus E protein protects from lethal infection in mice.. Virol J 2010 Jul 6;7:146.
                  doi: 10.1186/1743-422X-7-146pubmed: 20604940google scholar: lookup
                22. Rossi SL, Ross TM, Evans JD. West Nile virus.. Clin Lab Med 2010 Mar;30(1):47-65.
                  doi: 10.1016/j.cll.2009.10.006pubmed: 20513541google scholar: lookup
                23. Demento SL, Eisenbarth SC, Foellmer HG, Platt C, Caplan MJ, Mark Saltzman W, Mellman I, Ledizet M, Fikrig E, Flavell RA, Fahmy TM. Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy.. Vaccine 2009 May 18;27(23):3013-21.
                  doi: 10.1016/j.vaccine.2009.03.034pubmed: 19428913google scholar: lookup
                24. Guo X, Booth CJ, Paley MA, Wang X, DePonte K, Fikrig E, Narasimhan S, Montgomery RR. Inhibition of neutrophil function by two tick salivary proteins.. Infect Immun 2009 Jun;77(6):2320-9.
                  doi: 10.1128/IAI.01507-08pubmed: 19332533google scholar: lookup
                25. Bonafé N, Rininger JA, Chubet RG, Foellmer HG, Fader S, Anderson JF, Bushmich SL, Anthony K, Ledizet M, Fikrig E, Koski RA, Kaplan P. A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells.. Vaccine 2009 Jan 7;27(2):213-22.
                  doi: 10.1016/j.vaccine.2008.10.046pubmed: 18996430google scholar: lookup
                26. Magnarelli LA, Bushmich SL, Anderson JF, Ledizet M, Koski RA. Serum antibodies to West Nile virus in naturally exposed and vaccinated horses.. J Med Microbiol 2008 Sep;57(Pt 9):1087-1093.
                  doi: 10.1099/jmm.0.47849-0pubmed: 18719177google scholar: lookup
                27. Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR. Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderly.. J Virol 2008 Aug;82(15):7613-23.
                  doi: 10.1128/JVI.00618-08pubmed: 18508883google scholar: lookup
                28. Goncalvez AP, Chien CH, Tubthong K, Gorshkova I, Roll C, Donau O, Schuck P, Yoksan S, Wang SD, Purcell RH, Lai CJ. Humanized monoclonal antibodies derived from chimpanzee Fabs protect against Japanese encephalitis virus in vitro and in vivo.. J Virol 2008 Jul;82(14):7009-21.
                  doi: 10.1128/JVI.00291-08pubmed: 18480437google scholar: lookup
                29. Oliphant T, Nybakken GE, Austin SK, Xu Q, Bramson J, Loeb M, Throsby M, Fremont DH, Pierson TC, Diamond MS. Induction of epitope-specific neutralizing antibodies against West Nile virus.. J Virol 2007 Nov;81(21):11828-39.
                  doi: 10.1128/JVI.00643-07pubmed: 17715236google scholar: lookup
                30. Schepp-Berglind J, Luo M, Wang D, Wicker JA, Raja NU, Hoel BD, Holman DH, Barrett AD, Dong JY. Complex adenovirus-mediated expression of West Nile virus C, PreM, E, and NS1 proteins induces both humoral and cellular immune responses.. Clin Vaccine Immunol 2007 Sep;14(9):1117-26.
                  doi: 10.1128/CVI.00070-07pubmed: 17634508google scholar: lookup
                31. Bai F, Town T, Pradhan D, Cox J, Ashish, Ledizet M, Anderson JF, Flavell RA, Krueger JK, Koski RA, Fikrig E. Antiviral peptides targeting the west nile virus envelope protein.. J Virol 2007 Feb;81(4):2047-55.
                  doi: 10.1128/JVI.01840-06pubmed: 17151121google scholar: lookup
                32. Lieberman MM, Clements DE, Ogata S, Wang G, Corpuz G, Wong T, Martyak T, Gilson L, Coller BA, Leung J, Watts DM, Tesh RB, Siirin M, Travassos da Rosa A, Humphreys T, Weeks-Levy C. Preparation and immunogenic properties of a recombinant West Nile subunit vaccine.. Vaccine 2007 Jan 5;25(3):414-23.
                  doi: 10.1016/j.vaccine.2006.08.018pubmed: 16996661google scholar: lookup
                33. Samuel MA, Diamond MS. Pathogenesis of West Nile Virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion.. J Virol 2006 Oct;80(19):9349-60.
                  doi: 10.1128/JVI.01122-06pubmed: 16973541google scholar: lookup
                34. Gould LH, Sui J, Foellmer H, Oliphant T, Wang T, Ledizet M, Murakami A, Noonan K, Lambeth C, Kar K, Anderson JF, de Silva AM, Diamond MS, Koski RA, Marasco WA, Fikrig E. Protective and therapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virus.. J Virol 2005 Dec;79(23):14606-13.
                  doi: 10.1128/JVI.79.23.14606-14613.2005pubmed: 16282460google scholar: lookup
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