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Region(s) of Interest: United States, Missouri
Institution(s): Washington University School of Medicine in St. Louis
Mouse antibodies pinpoint Zika's weak spots
Antibodies that specifically protect against Zika infection have been
identified in mice, report Washington University School of Medicine in St.
Louis researchers on July 27 in Cell. This is the second publication in recent
weeks (another paper showing human Zika antibodies appeared in Science on
July 14, DOI: 10.1126/science.aaf8505) that explores the surfaces that the
antibodies target on the virus. The information will help inform the
development of vaccines, diagnostics, and antibody-based prophylactic and
therapeutic agents.
"Using biophysical methods, we clearly identified and characterized a panel
of Zika-specific antibodies in high resolution, and have developed a
correlation between the precise epitopes that are recognized and protection against the virus," says
immunologist Daved Fremont, co-senior author on the paper. "There have been a number of studies looking at
cross-reactive antibodies against Dengue and West Nile, but many of these therapeutic antibodies have been
viral specific, which have been difficult to isolate for Zika."
"We now have two groups that have come out with papers showing that antibodies that specifically recognize
Zika virus can protect against infection in vivo," says infectious disease researcher Michael Diamond, the
other co-author on the paper. "This is the first step toward optimizing current vaccine strategies and potentially
developing antibody-based therapeutics as well as augmenting efforts for generating diagnostics that would
specifically differentiate Zika viruses from other related flaviviruses." Antibody tests for Zika can be
unreliable because some
Zika antibodies can cross-react with other flaviviruses, such as Dengue virus and West Nile virus (hinting that
the antibodies target genetically distinct but structurally similar regions across this family of viruses).
Laboratories must use more expensive nucleic-acid-based tests, which look for the presence of viral particles,
in order to confirm Zika infection.
Fremont and Diamond's laboratory identified antibodies by infecting mice engineered to be susceptible to Zika
(DOI: 10.1016/j.chom.2016.03.010) with the virus and collecting their antibody-producing B cells. The
researchers then screened the antibodies against Zika surface proteins. Six candidate antibodies were found,
and from these, four were able to effectively prevent or treat Zika infection in cells and in mice. Haiyan Zhao,
first author and a postdoctoral researcher in Fremont's laboratory, took the lead on using X-ray crystallography
to visual the viral epitopes as well as directed the binding assays to characterize the antibodies.
"The other two families of epitopes that we uncovered in this study, the cryo-electron microscopy would tell
you are never exposed to the virus, so we call these cryptic epitopes," says Fremont, who has been
collaborating with Diamond on flavivirus research since 2003. "These results shed light on some of the
gymnastics that Zika viral particles probably go through during infection." Dengue virus is also known to have
these unexplained cryptic epitopes.
The researchers next want to identify at which stages of pregnancy the Zika antibodies have the most
protective effects against the virus. Although the antibodies were identified in mice, they can be humanized
without much difficulty, they say. InScience on July 14, Davide Corti of Humabs BioMed SA and Federica
Sallusto of the Institute for Research in Biomedicine in Bellinzona, Switzerland reported producing fully
human antibodies that could neutralize the Zika virus in mouse models, work Diamond says is quite
complementary to findings in the Cell paper.
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This work was supported by grants from the National Institutes of Health and the Center for Structural
Genomics of Infectious Diseases. Michael Diamond is a consultant for Inbios, Visterra, Sanofi, and Takeda
Pharmaceuticals, is on the Scientific Advisory Boards of Moderna and OraGene, and is a recipient of research
grants from Moderna, Sanofi, and Visterra.
Cell, Zhao and Fernandez et al.: "Structural basis of Zika virus specific antibody
protection" http://www.cell.com/cell/fulltext/S0092-8674(16)30927-8.
DOI: http://dx.doi.org/10.1016/j.cell.2016.07.020
Press Conference: Daved Fremont will discuss the work at a press conference at the EuroScience Open
Forum (ESOF 2016, http://www.esof.eu/) on July 27, 2016 at 9:00 am BST (4 am ET).
Author Contacts:
Daved H Fremont, Ph.D.
Professor, Departments of Pathology & Immunology,
Washington University School of Medicine
1-314-255-6171
fremont@wustl.ed
Michael S. Diamond, MD, PhD
Professor of Internal Medicine
Washington University School of Medicine
1-314-362-2842
diamond@borcim.wustl.edu
Media Contacts:
Tamara Bhandari, PhD
Senior Medical Science Writer
Washington University in St. Louis
1-314-286-0122
tbhandari@wustl.edu