{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:13:52Z","timestamp":1792844032406,"version":"4.5.0"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":45,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Naitonal Institute of Allergy and Infectious Diseases","award":["AI132246"],"award-info":[{"award-number":["AI132246"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging arboviral and zoonotic bunyavirus. CCHFV can infect livestock, wild animals, and humans. Here, we report the isolation of a panel of mAbs from the B cells of an immune individual following a natural nosocomial infection. We determined that the panel comprised antibodies that bound to 2 glycoproteins: (a) the carboxy-terminal glycoprotein (Gc) that serves as the fusion protein and (b) the glycoprotein 38 (GP38). By antibody variable gene analysis, we identified genetic diversity in the B cell response to CCHFV within a single donor for both Gc- and GP38-specific responses. Protection against most bunyavirus-associated diseases is mediated principally by neutralizing antibodies, but here, we found that neutralization activity was not associated with protection. Gc-specific antibodies to diverse antigenic sites neutralized only weakly and did not protect against heterologous virus challenge. GP38-specific antibodies bound to 2 dominant antigenic sites on the glycoprotein. Although GP38-specific antibodies did not neutralize the virus, one mediated protection against heterologous virus challenge in an experimental model of infection in mice primarily by complement-mediated activity. These studies support the development of protective CCHFV countermeasures against GP38.<\/jats:p>\n                  <jats:p>A human monoclonal antibody directed to the GP38 protein of Crimean-Congo hemorrhagic fever virus (CCHFV) does not neutralize the virus but mediates protection against heterologous virus challenge in an experimental model of infection in mice. The studies reveal novel aspects of mechanisms of bunyavirus immunity.<\/jats:p>","DOI":"10.1172\/jci191440","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:00:17Z","timestamp":1774972817000},"source":"Crossref","is-referenced-by-count":3,"title":["Human antibody targeting Crimean-Congo hemorrhagic fever virus glycoprotein 38 protects mice against heterologous virus challenge"],"prefix":"10.1172","volume":"136","author":[{"given":"Nathaniel S.","family":"Chapman","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology and"},{"name":"The Vanderbilt Center for Antibody Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoriya","family":"Borisevich","sequence":"additional","affiliation":[{"name":"Galveston National Laboratory and"},{"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurgun","family":"Kose","sequence":"additional","affiliation":[{"name":"The Vanderbilt Center for Antibody Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1132-2550","authenticated-orcid":true,"given":"Luke","family":"Myers","sequence":"additional","affiliation":[{"name":"The Vanderbilt Center for Antibody Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Priest","sequence":"additional","affiliation":[{"name":"The Vanderbilt Center for Antibody Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9ric","family":"Bergeron","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA."},{"name":"Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Trigo Esteban","sequence":"additional","affiliation":[{"name":"National Referral Centre for Tropical Diseases and International Health, Hospital La Paz\u2013Carlos III, IdIPaz, CIBERInfec, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Paz","family":"S\u00e1nchez-Seco","sequence":"additional","affiliation":[{"name":"Laboratory of Arbovirus and Imported Viral Diseases, National Center of Microbiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Melero","sequence":"additional","affiliation":[{"name":"Laboratory of Arbovirus and Imported Viral Diseases, National Center of Microbiology, and"},{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Geisbert","sequence":"additional","affiliation":[{"name":"Galveston National Laboratory and"},{"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7718-1522","authenticated-orcid":true,"given":"Robert W.","family":"Cross","sequence":"additional","affiliation":[{"name":"Galveston National Laboratory and"},{"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0049-1079","authenticated-orcid":true,"suffix":"Jr.","given":"James E.","family":"Crowe","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology and"},{"name":"The Vanderbilt Center for Antibody Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."},{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.07.006"},{"key":"B2","unstructured":"Center for Disease Control and Prevention (CDC). Crimean-Congo Hemorrhagic Fever (CCHF). https:\/\/www.cdc.gov\/crimean-congo-hemorrhagic\/about\/index.html Updated March 5, 2024. Accessed September 2, 2024"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70435-2"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2019.12.001"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615162"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2024.29.6.2400023"},{"key":"B7","unstructured":"Dire\u00e7\u00e3o-Geral da Sa\u00fade. Crimean-Congo haemorrhagic fever case confirmed in Portugal. https:\/\/www.dgs.pt\/em-destaque\/confirmacao-de-caso-de-febre-hemorragica-de-crimeia-congo-em-portugal-.aspx Updated 2024. Accessed March 30, 2026"},{"key":"B8","unstructured":"The World Health Organization R&D Blueprint Team. 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