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

First Author  Gilchuk I Year  2016
Journal  Cell Volume  167
Issue  3 Pages  684-694.e9
PubMed ID  27768891 Mgi Jnum  J:357922
Mgi Id  MGI:6389963 Doi  10.1016/j.cell.2016.09.049
Citation  Gilchuk I, et al. (2016) Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections. Cell 167(3):684-694.e9
abstractText  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.
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