Human monoclonal antibodies prevent Zika virus escape mutations
 | Figure: FAB
Z021 bound to Zika envelope protein, EDIII (top); overlapping epitopes
on Zika EDIII (bottom). |
Pamela Bjorkman group (California Institute of Technology) and collaborators
Zika virus is a mosquito-borne flavivirus that usually
causes mild symptoms in infected individuals, but can result in
devastating neurological outcomes to babies born to women infected
during pregnancy. Vaccine development for Zika and other flaviviruses
is hindered by concerns of antibody-dependent enhancement (ADE), in
which antibodies that bind but do not neutralize can enhance instead of
prevent infection. To avoid concerns about ADE, passive transfer of
potent antibodies may provide a safe and effective alternative to
vaccination. Pamela Bjorkman and her group at Caltech determined the
crystal structures of the potent human monoclonal antibody Z021 bound
to its antigen in the Zika envelope protein (EDIIIZIKV) and in the
dengue 1 envelope protein (EDIIIDENV1). The structures show that the
Z021 antibody recognizes the two flaviviruses similarly, binding to the
lateral ridge of the EDIIIs. Collaborators at Rockefeller University
and the California National Primate Research Center at University of
California, Davis showed that Z021, in combination with another potent
human antibody, Z004, which recognizes a distinct but overlapping
epitope, decreased viremia and prevented Zika viral escape in a
non-human primate model. Although sterilizing protection was not
reached in this high-dose challenge, the study aids our understanding
of cross-reactivity of anti-flavivirus antibodies and of viral escape
in the context of antibody pre-exposure prophylaxis.
Citation: 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, Coffey, LL, MacDonald, MR, Bjorkman, PM, Nussenzweig, MC,
Robbiani, DF, A combination of two human monoclonal antibodies prevents
Zika virus escape mutations in non-human primates, Cell Reports
25, 1385-1394 (2018). DOI: 10.1016/j.celrep.2018.10.031
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