Cell · 2016
Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gilchuk Iuliia, Gilchuk Pavlo, Sapparapu Gopal, Lampley Rebecca, Singh Vidisha, Kose Nurgun, Blum David L, Hughes Laura J, Satheshkumar Panayampalli S, Townsend Michael B, Kondas Ashley V, Reed Zachary, Weiner Zachary, Olson Victoria A, Hammarlund Erika, Raue Hans-Peter, Slifka Mark K, Slaughter James C, Graham Barney S, Edwards Kathryn M, Eisenberg Roselyn J, Cohen Gary H, Joyce Sebastian, Crowe James E
Аннотация
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.