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 Schneider & 4 others Margaret R. MacDonald, Pamela J. Bjorkman, Michel C. Nussenzweig, Davide F. Robbiani

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Pages1385-1394.e7
JournalCell Reports
Volume25
Issue number6
DOIs
StatePublished - Nov 6 2018

Fingerprint

Viruses
Primates
Monoclonal Antibodies
Mutation
Macaca
Antibodies
Viremia
Vaccines
Dengue Virus
Virus Diseases
Nervous System
Zika Virus
Aberrations
Epitopes
Safety

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Keeffe, J. R., Van Rompay, K. K. A., Olsen, P. C., Wang, Q., Gazumyan, A., Azzopardi, S. A., ... 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

A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. / 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.; Schneider, Lark L; MacDonald, Margaret R.; Bjorkman, Pamela J.; Nussenzweig, Michel C.; Robbiani, Davide F.

In: Cell Reports, Vol. 25, No. 6, 06.11.2018, p. 1385-1394.e7.

Research output: Contribution to journalArticle

Keeffe, JR, Van Rompay, KKA, Olsen, PC, Wang, Q, Gazumyan, A, Azzopardi, SA, Schaefer-Babajew, D, Lee, YE, Stuart, JB, Singapuri, A, Watanabe, J, Usachenko, J, Ardeshir, A, Saeed, M, Agudelo, M, Eisenreich, T, Bournazos, S, Oliveira, TY, Rice, CM, Schneider, LL, MacDonald, MR, Bjorkman, PJ, Nussenzweig, MC & Robbiani, DF 2018, 'A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates' Cell Reports, vol. 25, no. 6, pp. 1385-1394.e7. https://doi.org/10.1016/j.celrep.2018.10.031
Keeffe JR, Van Rompay KKA, Olsen PC, Wang Q, Gazumyan A, Azzopardi SA et al. A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. Cell Reports. 2018 Nov 6;25(6):1385-1394.e7. https://doi.org/10.1016/j.celrep.2018.10.031
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. ; Schneider, Lark L ; MacDonald, Margaret R. ; Bjorkman, Pamela J. ; Nussenzweig, Michel C. ; Robbiani, Davide F. / A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. In: Cell Reports. 2018 ; Vol. 25, No. 6. pp. 1385-1394.e7.
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