title: Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
abstract: Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.
authors: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Iuliia
authors: I
authors: Gilchuk
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Veterans Administration Tennessee Valley Healthcare System, Nashville, TN 37332, USA.
authors: Pavlo
authors: P
authors: Gilchuk
authors: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Gopal
authors: G
authors: Sapparapu
authors: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Rebecca
authors: R
authors: Lampley
authors: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Vidisha
authors: V
authors: Singh
authors: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Nurgun
authors: N
authors: Kose
authors: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: David L
authors: DL
authors: Blum
authors: Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Laura J
authors: LJ
authors: Hughes
authors: Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Panayampalli S
authors: PS
authors: Satheshkumar
authors: Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Michael B
authors: MB
authors: Townsend
authors: Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Ashley V
authors: AV
authors: Kondas
authors: Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA; Laboratory Leadership Service, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Zachary
authors: Z
authors: Reed
authors: Laboratory Leadership Service, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Zachary
authors: Z
authors: Weiner
authors: Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Victoria A
authors: VA
authors: Olson
authors: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
authors: Erika
authors: E
authors: Hammarlund
authors: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
authors: Hans-Peter
authors: HP
authors: Raue
authors: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
authors: Mark K
authors: MK
authors: Slifka
authors: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: James C
authors: JC
authors: Slaughter
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors: Barney S
authors: BS
authors: Graham
authors: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Kathryn M
authors: KM
authors: Edwards
authors: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Roselyn J
authors: RJ
authors: Eisenberg
authors: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Gary H
authors: GH
authors: Cohen
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Veterans Administration Tennessee Valley Healthcare System, Nashville, TN 37332, USA.
authors: Sebastian
authors: S
authors: Joyce
authors: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.
authors: James E
authors: JE
authors: Crowe
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D015605:Cowpox / Q000276:immunology; D015608:Cowpox virus / Q000276:immunology; D003429:Cross Reactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D045908:Mpox, Monkeypox / Q000276:immunology; D008993:Monkeypox virus / Q000276:immunology; D011213:Poxviridae Infections / Q000276:immunology*; D012899:Smallpox / Q000276:immunology; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D012901:Variola virus / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: antigen specificity; cross-neutralization; human monoclonal antibodies; poxvirus infections; protective immunity; smallpox vaccine