4.8 Article

Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques

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SCIENCE TRANSLATIONAL MEDICINE
卷 9, 期 410, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aan8184

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资金

  1. NIH [4P01AI094420-05, P30AI073961, P51 OD011132]
  2. Wallace H. Coulter Center for Translational Research at the University of Miami
  3. Miami Clinical and Translational Science Institute (CTSI)
  4. National Institute of Allergy and Infectious Diseases, NIH
  5. Defense Advanced Research Projects Agency (DARPA) Autonomous Diagnostics to Enable Prevention and Therapeutics: Prophylactic Options to Environmental and Contagious Threats (ADEPT-PROTECT) program [W31P4Q-13-1-0011]

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Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasma-blasts of a ZIKV-infected patient-SMZAb1, SMZAb2, and SMZAb5-directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fc gamma receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge. Given that numerous antibodies have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses.

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