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

Jennifer R. Keeffe, Koen K.A. Van Rompay, Priscilla C. Olsen, Qiao Wang, Anna Gazumyan, Stephanie A. Azzopardi, Dennis Schaefer-Babajew, Yu E. Lee, Jackson B. Stuart, Anil Singapuri, Jennifer Watanabe, Jodie Usachenko, Amir Ardeshir, Mohsan Saeed, Marianna Agudelo, Thomas Eisenreich, Stylianos Bournazos, Thiago Y. Oliveira, Charles M. Rice, Lark L SchneiderMargaret R. MacDonald, Pamela J. Bjorkman, Michel C. Nussenzweig, Davide F. Robbiani

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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. Passive administration of anti-Zika human monoclonal antibodies could be an efficacious and safe alternative to vaccines for at-risk populations. Keeffe et al. show that administration of a combination of two monoclonal antibodies to macaques followed by high-dose intravenous Zika challenge reduces viremia and prevents the emergence of viral escape mutations.

Original languageEnglish (US)
Pages (from-to)1385-1394.e7
JournalCell Reports
Volume25
Issue number6
DOIs
StatePublished - Nov 6 2018

Keywords

  • antibodies
  • antibody dependent enhancement
  • crystal structure
  • epitope
  • escape
  • flavivirus
  • macaques
  • prophylaxis
  • protection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Keeffe, J. R., Van Rompay, K. K. A., Olsen, P. C., Wang, Q., Gazumyan, A., Azzopardi, S. A., Schaefer-Babajew, D., Lee, Y. E., Stuart, J. B., Singapuri, A., Watanabe, J., Usachenko, J., Ardeshir, A., Saeed, M., Agudelo, M., Eisenreich, T., Bournazos, S., Oliveira, T. Y., Rice, C. M., ... Robbiani, D. F. (2018). A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. Cell Reports, 25(6), 1385-1394.e7. https://doi.org/10.1016/j.celrep.2018.10.031