{
    "abstract": "Crimean-Congo hemorrhagic fever virus (CCHFV) is an enveloped, negative-sense RNA virus that is spread by ticks across Europe, Africa, and Asia and causes a lethal disease in humans (~30%-40% case fatality). There are currently no approved vaccines or therapeutics. Antibody-based therapeutics targeting the CCHFV surface glycoproteins Gn and Gc, which are responsible for viral attachment and fusion during entry, are a promising therapeutic approach. We previously isolated three broadly neutralizing Gc-targeting human monoclonal antibodies (mAbs) and showed certain cocktails of these mAbs demonstrated synergistic virus neutralization. Furthermore, physical linkage of two of these mAbs into a dual variable domain (DVD) bispecific antibody (bsAb) DVD-121-801 resulted in improved neutralization and therapeutic protection against a lethal CCHFV challenge in mice. However, the molecular requirements for the activity of DVD-121-801, and why it is augmented over monospecific parental mAbs, remain the topic of investigation. Here, we generated a new panel of bsAb variants of DVD-121-801 to explore the spacing and avidity requirements and further optimize its protective efficacy against divergent CCHFV isolates. We evaluated these variants for neutralization, fusion inhibition, and protection with virus-like particles, authentic viruses, and ",
    "authors": [
        {
            "affiliation": "Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "Albert",
            "initials": "A",
            "lastname": "Wang"
        },
        {
            "affiliation": "Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.\nGeneva Foundation, Tacoma, Washington, USA.",
            "firstname": "Stephanie R",
            "initials": "SR",
            "lastname": "Monticelli"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "Ariel S",
            "initials": "AS",
            "lastname": "Wirchnianski"
        },
        {
            "affiliation": "Mapp Biopharmaceutical, Inc., San Diego, California, USA.",
            "firstname": "Dafna M",
            "initials": "DM",
            "lastname": "Abelson"
        },
        {
            "affiliation": "Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.",
            "firstname": "Ana I",
            "initials": "AI",
            "lastname": "Kuehne"
        },
        {
            "affiliation": "Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.",
            "firstname": "Russell R",
            "initials": "RR",
            "lastname": "Bakken"
        },
        {
            "affiliation": "Mapp Biopharmaceutical, Inc., San Diego, California, USA.",
            "firstname": "Marissa",
            "initials": "M",
            "lastname": "Middlecamp"
        },
        {
            "affiliation": "Mapp Biopharmaceutical, Inc., San Diego, California, USA.",
            "firstname": "Michael",
            "initials": "M",
            "lastname": "Weingart"
        },
        {
            "affiliation": "Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "Olivia",
            "initials": "O",
            "lastname": "Vergnolle"
        },
        {
            "affiliation": "Mapp Biopharmaceutical, Inc., San Diego, California, USA.",
            "firstname": "Zachary A",
            "initials": "ZA",
            "lastname": "Bornholdt"
        },
        {
            "affiliation": "Mapp Biopharmaceutical, Inc., San Diego, California, USA.",
            "firstname": "Crystal L",
            "initials": "CL",
            "lastname": "Moyer"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "Jacob L",
            "initials": "JL",
            "lastname": "Berrigan"
        },
        {
            "affiliation": "Mapp Biopharmaceutical, Inc., San Diego, California, USA.",
            "firstname": "Brandyn R",
            "initials": "BR",
            "lastname": "West"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "J Maximilian",
            "initials": "JM",
            "lastname": "Fels"
        },
        {
            "affiliation": "Mapp Biopharmaceutical, Inc., San Diego, California, USA.",
            "firstname": "Larry",
            "initials": "L",
            "lastname": "Zeitlin"
        },
        {
            "affiliation": "Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.",
            "firstname": "Andrew S",
            "initials": "AS",
            "lastname": "Herbert"
        },
        {
            "affiliation": "Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "Kartik",
            "initials": "K",
            "lastname": "Chandran"
        },
        {
            "affiliation": "Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "Chowdhury Raihan",
            "initials": "CR",
            "lastname": "Bikash"
        },
        {
            "affiliation": "Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.",
            "firstname": "Jonathan R",
            "initials": "JR",
            "lastname": "Lai"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.1128/mbio.03202-24",
    "journal": "mBio",
    "keywords": [
        "Crimean-Congo hemorrhagic fever virus",
        "bispecific antibody",
        "immunotherapy",
        "monoclonal antibody"
    ],
    "methods": null,
    "publication_date": "2025-04-16",
    "pubmed_id": "40237506",
    "results": null,
    "title": "Avidity and variable domain spacing strongly influence the therapeutic potency of bispecific antibodies against Crimean-Congo hemorrhagic fever virus.",
    "xml": "<Element 'PubmedArticle' at 0x788504640590>"
}