A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates

Details

• Alternative Title:
  Cell Rep
• Personal Author:
  Keeffe, Jennifer R. ; Van Rompay, Koen K.A. ; Olsen, Priscilla C. ; Wang, Qiao ; Gazumyan, Anna ; Azzopardi, Stephanie A. ; Schaefer-Babajew, Dennis ; Lee, Yu E. ; Stuart, Jackson B. ; Singapuri, Anil ; Watanabe, Jennifer ; Usachenko, Jodie ; Ardeshir, Amir ; Saeed, Mohsan ; Agudelo, Marianna ; Eisenreich, Thomas ; Bournazos, Stylianos ; Oliveira, Thiago Y. ; Rice, Charles M. ; Coffey, Lark L. ; MacDonald, Margaret R. ; Bjorkman, Pamela J. ; Nussenzweig, Michel C. ; Robbiani, Davide F.
• Description:
  Zika virus (ZIKV) causes severe neurologic complications and fetal aberrations. Vaccine development is hindered by potential safety concerns due to antibody cross-reactivity with dengue virus and the possibility of disease enhancement. In contrast, passive administration of anti-ZIKV antibodies engineered to prevent enhancement may be safe and effective. Here, we report on human monoclonal antibody Z021, a potent neutralizer that recognizes an epitope on the lateral ridge of the envelope domain III (EDIII) of ZIKV and is protective against ZIKV in mice. When administered to macaques undergoing a high-dose ZIKV challenge, a single anti-EDIII antibody selected for resistant variants. Co-administration of two antibodies, Z004 and Z021, which target distinct sites on EDIII, was associated with a delay and a 3- to 4-log decrease in peak viremia. Moreover, the combination of these antibodies engineered to avoid enhancement prevented viral escape due to mutation in macaques, a natural host for ZIKV.
• Subjects:
  Article
• Source:
  Cell Rep. 25(6):1385-1394.e7
• Pubmed ID:
  30403995
• Pubmed Central ID:
  PMC6268006
• Document Type:
  Journal Article
• Funding:
  R01 AI037526/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; UM1 AI100663/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; T32 AI070084/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; P51 OD011107/ODCDC CDC HHS/Office of the Director/United States ; U19 AI057229/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; UL1 TR001866/NCATS NIH HHS/National Center for Advancing Translational Sciences/United States ; R01 AI124690/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; P01 AI138938/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; R21 AI129479/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; R37 AI037526/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; U19 AI111825/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States
• Volume:
  25
• Issue:
  6
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5c7bb7bfd38c84798acd02782ba9a0b6b35bd333404b1eb48346cffffffcf4d2
• Download URL:
  https://stacks.cdc.gov/view/cdc/80488/cdc_80488_DS1.pdf
• File Type:
  [PDF - 1.99 MB ]