Researchers at Vanderbilt University Medical Center and Washington University School of Medicine in St. Louis have isolated a human monoclonal antibody that in a mouse model “markedly reduced” infection by the Zika virus.
The antibody, called ZIKV-117, also protected the fetus in pregnant mice infected with the virus, the researchers reported today in the journal Nature. Zika is believed to cause microcephaly, unusually small heads, and other congenital malformations in children born to infected women.
Similar protection studies in primates are warranted, and if the findings hold up, ZIKV-177 could be developed as a protective antibody treatment for pregnant women at risk of Zika infection, the researchers concluded.
The findings may also aid efforts to develop an effective anti-Zika vaccine, said James Crowe Jr., M.D., director of the Vanderbilt Vaccine Center and co-corresponding author of the paper with Michael S. Diamond, M.D., Ph.D., at Washington University.
“These naturally occurring human antibodies isolated from humans represent the first medical intervention that prevents Zika infection and damage to fetuses,” said Crowe, who also is Ann Scott Carell Professor in the Departments of Pediatrics and Pathology, Microbiology & Immunology in the Vanderbilt University School of Medicine.
“We’re excited because the data suggests we may have antibody treatments in hand that could be developed for use in pregnant women,” he said.
“The remarkable potency and breadth of inhibition by ZIKV-117 has great promise,” Diamond said, “as it was able to inhibit infection by strains from both Africa and America in cell culture and in animals, including during pregnancy.”
Diamond is associate director of The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs at Washington University.
Zika is a mosquito-borne virus that has emerged as a global public health threat. In addition to its association with congenital birth defects, Zika has been linked to Guillain-Barre syndrome, a neurological disorder that can lead to paralysis and death.
Since a major outbreak was reported in Brazil last year, Zika infections transmitted by mosquitoes have been reported throughout Africa, Asia, the Pacific, and the Americas, including Miami-Dade County, Florida.
During the past 15 years, Crowe and his colleagues have developed a high-efficiency method for isolating human monoclonal antibodies that can neutralize a wide range of viruses, from Ebola to HIV.
The Crowe and Diamond laboratories have collaborated recently on several projects including the generation of protective human monoclonal antibodies against Dengue, West Nile, Chikungunya and now Zika viruses.
Monoclonal antibodies are made from a single clone of B cells, a type of white blood cell, that have been fused to myeloma (cancer) cells to form fast-growing “hybridomas.” This allows researchers to quickly generate large quantities of antibodies against specific viral targets.
In the current study, the researchers isolated antibodies from the blood of people who’d been previously infected with the Zika virus in different parts of the world. The antibodies reacted to the envelope or “E” protein on the surface of the virus.
The researchers then generated a variety of monoclonal antibodies. In cell culture studies, they identified one, ZIKV-117, which broadly neutralized several different strains of the virus. In mice infected by the Zika virus, injection of the antibody markedly reduced disease and mortality, and reduced transmission from mother to fetus.
A team led by Purdue University researchers is the first to determine the structure of the Zika virus, which reveals insights critical to the development of effective antiviral treatments and vaccines.
The team also identified regions within the Zika virus structure where it differs from other flaviviruses, the family of viruses to which Zika belongs that includes dengue, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitic viruses.
A paper detailing the findings was published Thursday (March 31) in the journal Science and is available online.
Any regions within the virus structure unique to Zika have the potential to explain differences in how a virus is transmitted and how it manifests as a disease, said Richard Kuhn, director of the Purdue Institute for Inflammation, Immunology and Infectious Diseases (PI4D) who led the research team with Michael Rossmann, Purdue’s Hanley Distinguished Professor of Biological Sciences.
“The structure of the virus provides a map that shows potential regions of the virus that could be targeted by a therapeutic treatment, used to create an effective vaccine or to improve our ability to diagnose and distinguish Zika infection from that of other related viruses,” said Kuhn, who also is head of Purdue’s Department of Biological Sciences. “Determining the structure greatly advances our understanding of Zika – a virus about which little is known. It illuminates the most promising areas for further testing and research to combat infection.”
The Zika virus, a mosquito-borne disease, has recently been associated with a birth defect called microcephaly that causes brain damage and an abnormally small head in babies born to mothers infected during pregnancy. It also has been associated with the autoimmune disease Guillain-Barré syndrome, which can lead to temporary paralysis. In the majority of infected individuals symptoms are mild and include fever, skin rashes and flulike illness, according to the World Health Organization.
Zika virus transmission has been reported in 33 countries. Of the countries where Zika virus is circulating 12 have reported an increased incidence of Guillain-Barré syndrome, and Brazil and French Polynesia have reported an increase in microcephaly, according to WHO. In February WHO declared the Zika virus to be “a public health emergency of international concern.”
“This breakthrough illustrates not only the importance of basic research to the betterment of human health, but also its nimbleness in quickly addressing a pressing global concern,” said Purdue President Mitch Daniels. “This talented team of researchers solved a very difficult puzzle in a remarkably short period of time, and have provided those working on developing vaccines and treatments to stop this virus a map to guide their way.”
Rossmann and Kuhn collaborated with Theodore Pierson, chief of the viral pathogenesis section of the Laboratory of Viral Diseases at the National Institutes of Health National Institute of Allergy and Infectious Diseases. Additional research team members include Purdue graduate student Devika Sirohi and postdoctoral research associates Zhenguo Chen, Lei Sun and Thomas Klose.
The team’s paper marks the first published success of the new Purdue Institute for Inflammation, Immunology and Infectious Diseases in Purdue’s Discovery Park.