Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections

Iuliia Gilchuk, Pavlo Gilchuk, Gopal Sapparapu, Rebecca Lampley, Vidisha Singh, Nurgun Kose, David L. Blum, Laura J. Hughes, Panayampalli S. Satheshkumar, Michael B. Townsend, Ashley V. Kondas, Zachary Reed, Zachary Weiner, Victoria A. Olson, Erika Hammarlund, Hans Peter Raue, Mark K. Slifka, James C. Slaughter, Barney S. Graham, Kathryn M. EdwardsRoselyn J. Eisenberg, Gary H. Cohen, Sebastian Joyce, James E. Crowe

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)684-694.e9
JournalCell
Volume167
Issue number3
DOIs
StatePublished - Oct 20 2016

Keywords

  • antigen specificity
  • cross-neutralization
  • human monoclonal antibodies
  • poxvirus infections
  • protective immunity
  • smallpox vaccine

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections'. Together they form a unique fingerprint.

Cite this