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Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.

Cell | Oct 20, 2016

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.

Pubmed ID: 27768891 RIS Download

Mesh terms: Antibodies, Monoclonal | Antibodies, Neutralizing | Antibodies, Viral | Antibody Specificity | Cowpox | Cowpox virus | Cross Reactions | Humans | Leukocytes, Mononuclear | Monkeypox | Monkeypox virus | Poxviridae Infections | Smallpox | Vaccinia | Vaccinia virus | Variola virus

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Associated grants

  • Agency: NIH HHS, Id: P51 OD011092
  • Agency: NCATS NIH HHS, Id: UL1 TR000445
  • Agency: BLRD VA, Id: I01 BX001444
  • Agency: NIDDK NIH HHS, Id: P30 DK058404
  • Agency: NIAID NIH HHS, Id: U01 AI48512
  • Agency: NIAID NIH HHS, Id: U19 AI109948
  • Agency: NCI NIH HHS, Id: P30 CA068485
  • Agency: NCRR NIH HHS, Id: UL1 RR024975
  • Agency: NIAID NIH HHS, Id: HHSN272200900047C
  • Agency: NIAID NIH HHS, Id: U01 AI048512

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