{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:35:56Z","timestamp":1791653756891,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T00:00:00Z","timestamp":1521849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joint Science and Technology Office for Chemical and Biological Defense Program","award":["CB3957"],"award-info":[{"award-number":["CB3957"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Western equine encephalitis virus (WEEV) causes symptoms in humans ranging from mild febrile illness to life-threatening encephalitis, and no human medical countermeasures are licensed. A previous study demonstrated that immune serum from vaccinated mice protected against lethal WEEV infection, suggesting the utility of antibodies for pre- and post-exposure treatment. Here, three neutralizing and one binding human-like monoclonal antibodies were evaluated against WEEV aerosol challenge. Dose-dependent protection was observed with two antibodies administered individually, ToR69-3A2 and ToR68-2C3. In vitro neutralization was not a critical factor for protection in this murine model, as ToR69-3A2 is a strong neutralizing antibody, and ToR68-2C3 is a non-neutralizing antibody. This result highlights the importance of both neutralizing and non-neutralizing antibodies in the protection of mice from WEEV lethality.<\/jats:p>","DOI":"10.3390\/v10040147","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T03:43:29Z","timestamp":1522035809000},"page":"147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Human-Like Neutralizing Antibodies Protect Mice from Aerosol Exposure with Western Equine Encephalitis Virus"],"prefix":"10.3390","volume":"10","author":[{"given":"Crystal","family":"Burke","sequence":"first","affiliation":[{"name":"United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Froude","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Miethe","sequence":"additional","affiliation":[{"name":"Technische Universit\u00e4t Braunschweig, Institut f\u00fcr Biochemie, Biotechnologie und Bioinformatik, Spielmannstr.7, 38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"H\u00fclseweh","sequence":"additional","affiliation":[{"name":"Wehrwissenschaftliches Institut f\u00fcr Schutztechnologien (WIS)\u2014ABC-Schutz, Humboldtstr. 1, 29623 Munster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3418-6045","authenticated-orcid":false,"given":"Michael","family":"Hust","sequence":"additional","affiliation":[{"name":"Technische Universit\u00e4t Braunschweig, Institut f\u00fcr Biochemie, Biotechnologie und Bioinformatik, Spielmannstr.7, 38106 Braunschweig, Germany"},{"name":"YUMAB GmbH, Science Campus Braunschweig S\u00fcd, Inhoffenstr.7, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Glass","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,24]]},"reference":[{"key":"ref_1","unstructured":"Knipe, D.M., and Howley, P.M. (2007). Alphaviruses. Fields' Virology, Lippincott Williams & Wilkins. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.1073\/pnas.85.16.5997","article-title":"Western equine encephalitis virus is a recombinant virus","volume":"85","author":"Hahn","year":"1988","journal-title":"Pro. Nat. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.vetmic.2009.08.023","article-title":"Encephalitic alphaviruses","volume":"140","author":"Zacks","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1128\/CMR.7.1.89","article-title":"Medically important arboviruses of the united states and canada","volume":"7","author":"Calisher","year":"1994","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1080\/20014091096774","article-title":"Biological weapons in the twentieth century: A review and analysis","volume":"27","author":"Leitenberg","year":"2001","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_6","unstructured":"(2018, February 13). Current Trends Arboviral Infections of the Central Nervous System\u2014United States, Available online: https:\/\/www.cdc.gov\/mmwr\/preview\/mmwrhtml\/00001082.htm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.2460\/javma.1977.170.12.1396","article-title":"Western equine encephalomyelitis in horses in the northern red river valley, 1975","volume":"170","author":"Potter","year":"1977","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.2307\/4583872","article-title":"Epidemic of infectious encephalitis","volume":"56","author":"Leake","year":"1941","journal-title":"Public Health Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3201\/eid1705.101068","article-title":"Fatal human case of western equine encephalitis, uruguay","volume":"17","author":"Delfraro","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6295","DOI":"10.4049\/jimmunol.1300304","article-title":"An essential role of antibodies in the control of chikungunya virus infection","volume":"190","author":"Lum","year":"2013","journal-title":"J. Immunol."},{"key":"ref_11","first-page":"191","article-title":"Role of antibodies in controlling alphavirus infection of neurons","volume":"260","author":"Griffin","year":"2001","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1658936","article-title":"Antibody-mediated clearance of alphavirus infection from neurons","volume":"254","author":"Levine","year":"1991","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.virol.2016.08.023","article-title":"Venezuelan and western equine encephalitis virus e1 liposome antigen nucleic acid complexes protect mice from lethal challenge with multiple alphaviruses","volume":"499","author":"Rico","year":"2016","journal-title":"Virology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1128\/JVI.02297-13","article-title":"Liposome-antigen-nucleic acid complexes protect mice from lethal challenge with western and eastern equine encephalitis viruses","volume":"88","author":"Phillips","year":"2014","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1016\/j.vaccine.2007.03.042","article-title":"Complete protection of mice against a lethal dose challenge of western equine encephalitis virus after immunization with an adenovirus-vectored vaccine","volume":"25","author":"Wu","year":"2007","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0042-6822(85)90343-5","article-title":"The neutralization site on the e2 glycoprotein of venezuelan equine encephalomyelitis (TC-83) virus is composed of multiple conformationally stable epitopes","volume":"142","author":"Roehrig","year":"1985","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1099\/0022-1317-64-6-1405","article-title":"Neutralizing and non-neutralizing monoclonal antibodies to the e2 glycoprotein of semliki forest virus can protect mice from lethal encephalitis","volume":"64","author":"Boere","year":"1983","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5558","DOI":"10.1016\/j.vaccine.2010.06.038","article-title":"A recombinant humanized monoclonal antibody completely protects mice against lethal challenge with venezuelan equine encephalitis virus","volume":"28","author":"Hu","year":"2010","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"1Hulseweh, B., Rulker, T., Pelat, T., Langermann, C., Frenzel, A., Schirrmann, T., Dubel, S., Thullier, P., and Hust, M. (2014). Human-like antibodies neutralizing western equine encephalitis virus. MAbs, 6, 718\u2013727.","DOI":"10.4161\/mabs.28170"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rulker, T., Voss, L., Thullier, P., LM, O.B., Pelat, T., Perkins, S.D., Langermann, C., Schirrmann, T., Dubel, S., and Marschall, H.J. (2012). Isolation and characterisation of a human-like antibody fragment (SCFV) that inactivates veev in vitro and in vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037242"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kirsch, M.I., Hulseweh, B., Nacke, C., Rulker, T., Schirrmann, T., Marschall, H.J., Hust, M., and Dubel, S. (2008). Development of human antibody fragments using antibody phage display for the detection and diagnosis of venezuelan equine encephalitis virus (veev). BMC Biotechnol., 8.","DOI":"10.1186\/1472-6750-8-66"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jager, V., Bussow, K., Wagner, A., Weber, S., Hust, M., Frenzel, A., and Schirrmann, T. (2013). High level transient production of recombinant antibodies and antibody fusion proteins in hek293 cells. BMC Biotechnol., 13.","DOI":"10.1186\/1472-6750-13-52"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/19420862.2017.1299848","article-title":"Generation and characterization of protective antibodies to marburg virus","volume":"9","author":"Froude","year":"2017","journal-title":"MAbs"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Phelps, A.L., O'Brien, L.M., Eastaugh, L.S., Davies, C., Lever, M.S., Ennis, J., Zeitlin, L., Nunez, A., and Ulaeto, D.O. (2017). Susceptibility and lethality of western equine encephalitis virus in balb\/c mice when infected by the aerosol route. Viruses, 9.","DOI":"10.3390\/v9070163"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ko, S.Y.A.W., Yang, E.S., Kong, W.P., Burke, C.W., Honnold, S.P., Nichols, D.K., Schieber, G.L., Carlton, K., DaSilva, L., and Traina-Dorge, V. (2018). A trivalent virus-like particle vaccine protects against diverse equine encephalitis viruses in non-human primates, Manuscript in preparation.","DOI":"10.1126\/scitranslmed.aav3113"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1089\/bsp.2009.0032","article-title":"Alphavirus antiviral drug development: Scientific gap analysis and prospective research areas","volume":"7","author":"Reichert","year":"2009","journal-title":"Biosecur. Bioterror."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/297070a0","article-title":"Non-neutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis","volume":"297","author":"Schmaljohn","year":"1982","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12683","DOI":"10.1128\/JVI.01345-10","article-title":"Antibody to the e3 glycoprotein protects mice against lethal venezuelan equine encephalitis virus infection","volume":"84","author":"Parker","year":"2010","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"AID-0019\u20132014","DOI":"10.1128\/microbiolspec.AID-0019-2014","article-title":"Functions of antibodies","volume":"2","author":"Forthal","year":"2014","journal-title":"Microbiol. Spectr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.3389\/fimmu.2017.01590","article-title":"Non-neutralizing antibodies directed against hiv and their functions","volume":"8","author":"Mayr","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12077","DOI":"10.1128\/JVI.01406-14","article-title":"Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses","volume":"88","author":"Reed","year":"2014","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1086\/514240","article-title":"Immunologic interference from sequential administration of live attenuated alphavirus vaccines","volume":"177","author":"McClain","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.1016\/j.vaccine.2012.09.049","article-title":"Immune interference in the setting of same-day administration of two similar inactivated alphavirus vaccines: Eastern equine and western equine encephalitis","volume":"30","author":"Reisler","year":"2012","journal-title":"Vaccine"},{"key":"ref_34","unstructured":"Burke, C.W.P.A.I., Erwin-Cohen, R., Eccleston, L.T., Fitzpatrick, C.J., and Glass, P.J. (2018). A multi-agent alphavirus replicon particle vaccine is immunogenic and provides proection against western equine encephalitis disease in non-human primates, Manuscript in preparation."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gardner, C.L., Sun, C., Luke, T., Raviprakash, K., Wu, H., Jiao, J.A., Sullivan, E., Reed, D.S., Ryman, K.D., and Klimstra, W.B. (2017). Antibody preparations from human transchromosomic cows exhibit prophylactic and therapeutic efficacy against venezuelan equine encephalitis virus. J. Virol., 91.","DOI":"10.1128\/JVI.00226-17"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/j.celrep.2015.08.038","article-title":"Emergence of ebola virus escape variants in infected nonhuman primates treated with the mb-003 antibody cocktail","volume":"12","author":"Kugelman","year":"2015","journal-title":"Cell. Rep."},{"key":"ref_37","first-page":"344","article-title":"Monoclonal antibody-escape variant of dengue virus serotype 1: Genetic composition and envelope protein expression","volume":"32","author":"Chem","year":"2015","journal-title":"Trop. Biomed."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12364","DOI":"10.1128\/JVI.01381-14","article-title":"Epitope mapping of the hemagglutinin molecule of a\/(h1n1)pdm09 influenza virus by using monoclonal antibody escape mutants","volume":"88","author":"Matsuzaki","year":"2014","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8213","DOI":"10.1128\/JVI.01032-14","article-title":"Chikungunya viruses that escape monoclonal antibody therapy are clinically attenuated, stable, and not purified in mosquitoes","volume":"88","author":"Pal","year":"2014","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lee, C.Y., Kam, Y.W., Fric, J., Malleret, B., Koh, E.G., Prakash, C., Huang, W., Lee, W.W., Lin, C., and Lin, R.T. (2011). Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002390"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/4\/147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:58:23Z","timestamp":1760194703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/4\/147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,24]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4]]}},"alternative-id":["v10040147"],"URL":"https:\/\/doi.org\/10.3390\/v10040147","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,24]]}}}