{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:03:24Z","timestamp":1780563804451,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,1]]},"group-title":"Immunology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH, NIAID","award":["R01AI173084"],"award-info":[{"award-number":["R01AI173084"]}]},{"name":"NIH, NIAID","award":["R01AI175461"],"award-info":[{"award-number":["R01AI175461"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                  remains a global health threat, particularly to young children, the elderly, and immunocompromised individuals. Pneumococcal vaccines targeting the bacterial capsule polysaccharide do not protect against all 100+ pneumococcal serotypes, contributing to non-vaccine serotype infections and antibiotic resistance. To address these limitations, we isolated human monoclonal antibodies (mAbs) targeting pneumococcal surface proteins and identified a first-in-class mAb, derived from a patient with prior pneumococcal infection, namely mAb 5995-40. mAb 5995-40 bound multiple pneumococcal proteins, including PcpA and PspA, through a conserved choline-binding domain shared across serotypes. Functionally, mAb 5995-40 provided complete protection in lethal pneumococcal challenge models and improved survival in influenza A, influenza B, and respiratory syncytial virus-associated bacterial coinfection models. Mechanistic studies showed enhanced opsonophagocytic killing, reduced bacterial dissemination, and blocked epithelial translocation. Cryo-electron microscopy identified a repeating motif within the choline-binding domain targeted by mAb 5995-40, highlighting its potential as a broadly protective pneumococcal therapeutic.\n                <\/jats:p>","DOI":"10.64898\/2026.05.28.728567","type":"posted-content","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:20:11Z","timestamp":1780370411000},"source":"Crossref","is-referenced-by-count":0,"title":["A pan-serotype human monoclonal antibody protects against pneumococcal infection by targeting multiple choline binding domain proteins"],"prefix":"10.64898","author":[{"given":"Anna L.","family":"McCormick","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA"},{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrouz Ghazi","family":"Esfahani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA"},{"name":"Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline K.","family":"Page","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"},{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D.","family":"Shepard","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"},{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana G.","family":"Jop Vidal","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, and Center for Immunology and Microbial Research, School of Medicine, The University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn D.","family":"McCaffrey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Eun-Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-5588","authenticated-orcid":false,"given":"S. Mark","family":"Tompkins","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"},{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge E.","family":"Vidal","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, and Center for Immunology and Microbial Research, School of Medicine, The University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4709-2478","authenticated-orcid":false,"given":"Jarrod J.","family":"Mousa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA"},{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060401201580000_2026.05.28.728567v1.1","doi-asserted-by":"crossref","unstructured":"Huang, J. et al. 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