{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:08:45Z","timestamp":1791230925105,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Merck"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2023,12,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human metapneumovirus (hMPV) is a major respiratory pathogen worldwide. Here, we report the crystal structure of a neutralizing antibody M8C10 isolated from human B cells that targets the viral fusion protein (hMPV-F) trimerization interface. This is a novel prefusion-specific epitope that is highly conserved across hMPV strains and other related viruses. The interactions between M8C10 and hMPV-F are largely driven by residues on the light chain with most hypermutated light chain residues on or near the interface. This highlights the immune recognition of a buried trimerization interface during the\n            <jats:italic>in vivo<\/jats:italic>\n            affinity maturation process. In addition,\n            <jats:italic>in vivo<\/jats:italic>\n            cotton rat challenge studies were performed that show M8C10 provides strong lung protection against hMPV A viral challenge. The hMPV-F:M8C10 Fab structure reported reveals a class of hMPV antibodies in the human immune repertoire with a novel neutralization mechanism, targeting the trimerization interface of hMPV-F antigen.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Human metapneumovirus (hMPV) is a common pathogen causing lower respiratory tract infections worldwide and can develop severe symptoms in high-risk populations such as infants, the elderly, and immunocompromised patients. There are no approved hMPV vaccines or neutralizing antibodies available for therapeutic or prophylactic use. The trimeric hMPV fusion F protein is the major target of neutralizing antibodies in human sera. Understanding the immune recognition of antibodies to hMPV-F antigen will provide critical insights into developing efficacious hMPV monoclonal antibodies and vaccines.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01052-23","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T14:00:42Z","timestamp":1701352842000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Structural characterization of M8C10, a neutralizing antibody targeting a highly conserved prefusion-specific epitope on the metapneumovirus fusion trimerization interface"],"prefix":"10.1128","volume":"97","author":[{"given":"Xiao","family":"Xiao","sequence":"first","affiliation":[{"name":"Infectious Diseases and Vaccines Discovery, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"},{"name":"Discovery Biologics, Merck &amp; Co., Inc., Boston, Massachusetts, USA"},{"name":"MRL Postdoctoral Research Program, Merck &amp; Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Wen","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Vaccines Discovery, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Protein and Structural Chemistry, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Shipman","sequence":"additional","affiliation":[{"name":"Protein and Structural Chemistry, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Kostas","sequence":"additional","affiliation":[{"name":"Protein and Structural Chemistry, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Reid","sequence":"additional","affiliation":[{"name":"Protein and Structural Chemistry, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Warren","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Vaccines Discovery, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Tang","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Vaccines Discovery, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Luo","sequence":"additional","affiliation":[{"name":"Quantitative Biosciences, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Quantitative Biosciences, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Fridman","sequence":"additional","affiliation":[{"name":"Data Science and Scientific Informatics, Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Vaccines Discovery, Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpit A.","family":"Vora","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Vaccines Discovery, Merck &amp; Co., Inc., West Point, Pennsylvania, 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