Nav: Home

Mouse antibodies pinpoint Zika's weak spots

July 27, 2016

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 characterized a panel of Zika-specific antibodies and 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. "We found that our most protective antibodies bind the same region of the Zika virus that we and others have revealed for Dengue and West Nile, hinting that the humoral immune response targets genetically distinct, but structurally similar regions across this family of viruses."

"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. 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 visualize the viral epitopes as well as undertook binding assays to characterize the antibodies.

"The other two families of epitopes that we uncovered in this study, cryo-electron microscopy models of the mature virus would tell you are never exposed to antibodies, 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. In Science 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.
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"

Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit: To receive Cell Press media alerts, contact

Cell Press

Related Antibodies Articles:

Researchers discover first human antibodies that work against all ebolaviruses
After analyzing the blood of a survivor of the 2013-16 Ebola outbreak, a team of scientists from academia, industry and the government has discovered the first natural human antibodies that can neutralize and protect animals against all three major disease-causing ebolaviruses.
New method enables creation of better therapeutic antibodies
Researchers from the University of Maryland and Rockefeller University have refined a method to modify an antibody's sugar group structure, which plays a large role in determining an antibody's ability to activate the immune response.
Antibodies as 'messengers' in the nervous system
Antibodies are able to activate human nerve cells within milliseconds and hence modify their function -- that is the surprising conclusion of a study carried out at Human Biology at the Technical University of Munich (TUM).
Turning therapeutic antibodies inside-out to fight cancer
Researchers at the University of California, Riverside have camels and llamas to thank for their development of a new cancer treatment that is highly selective in blocking the action of faulty matrix metalloproteinases (MMPs).
Zika antibodies from infected patient thwart infection in mice
Researchers have identified neutralizing antibodies against Zika virus from an infected patient that fully protected mice from infection, adding to the current arsenal of antibodies in development for much needed antiviral therapies and vaccines.
A review on the therapeutic antibodies for spinal cord injury
Spinal cord injury (SCI) causes long-lasting damage in the spinal cord that leads to paraparesis, paraplegia, quadriplegia and other lifetime disabilities.
Training human antibodies to protect against HIV
During HIV infection, the virus mutates too rapidly for the immune system to combat, but some people produce antibodies that can recognize the virus even two years after infection.
How antiviral antibodies become part of immune memory
Emory scientists probe activated B cells, important for forming immune memory, during flu vaccination and infection and Ebola infection in humans.
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.
Antibodies identified that thwart Zika virus infection
Scientists at Washington University School of Medicine in St. Louis have identified antibodies capable of protecting against Zika virus infection, a significant step toward developing a vaccine, better diagnostic tests and possibly new antibody-based therapies.

Related Antibodies Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...