Human Antibody Against Zika Virus Offering New Promise

Findings also suggest the antibody might be especially effective because a lower concentration than expected is needed to inhibit a key mechanism of infection.
Findings also suggest the antibody might be especially effective because a lower concentration than expected is needed to inhibit a key mechanism of infection.

A team of researchers from 3 medical centers is reporting on a promising new avenue for combating Zika virus. It is theorized that neutralizing antibodies could be used to prevent and treat Zika virus infection. Now, investigators from Purdue University, Vanderbilt University Medical Center, and Washington University School of Medicine have identified the structure of a human antibody bound to the Zika virus and report on how the antibody interferes with the infection mechanism. Findings were reported in Nature Communications.

The investigators report on the structure of an infectious Zika virus strain (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. This naturally occurring fully human monoclonal antibody was isolated from a B cell in a peripheral blood sample obtained from an otherwise healthy subject with previous symptomatic Zika virus infection. The antibody was able to prevent fetal infection and demise in mice.

"We determined how 1 specific antibody neutralizes Zika virus. This has been a good experience that will guide our further investigation in how other antibodies neutralize the virus," study investigator Michael Rossmann, PhD, a professor of biological sciences at Purdue University, West Lafayette, Indiana, told Infectious Disease Advisor.

At this time, there is an urgent need to combat Zika virus, which can result in microcephaly in babies born to infected mothers. Babies with microcephaly can have a number of problems, including a small brain and head, developmental delays, seizures, vision and hearing loss, and feeding difficulty. The Zika virus also has been associated with Guillain-Barré syndrome.

Study investigator Richard Kuhn, PhD, director of the Purdue Institute of Inflammation, Immunology and Infectious Disease, said the new findings may help with the development of antiviral drugs. In addition, he said they also may help researchers identify important sites on the virus for human antibodies to hook onto, paving the way for a Zika virus vaccine.

"The message is that this gives us insight how vaccines might work," Dr Kuhn said in an interview with Infectious Disease Advisor. "It certainly appears to be effective in a mouse model, but whether it has a similar impact in humans is another story. There is a good hope that it will work in humans, but that has to be determined in clinical trials."

The first major outbreak of the Zika virus was recorded in Micronesia in 2007. Another outbreak started in 2014 in Brazil and quickly spread to the Caribbean and North America. During this past year, 4 cases of microcephaly were reported in New York City.

Zika is a flavivirus, similar to West Nile, yellow fever, Japanese encephalitis, and tick-borne encephalitic viruses. Flaviviruses are spread mainly by insects; however, Zika virus also can be transmitted sexually and from mother to child, note the researchers. The investigators said the new insights from this current investigation into Zika virus may also help in combating other flaviviruses.

"These findings can enhance our understanding of related flaviviruses by providing insight into useful epitopes that can be targeted. Although the exact residues may differ between viruses, the understanding of interactions can be utilized in order to improve vaccine design," study investigator Estefania Fernandez, a predoctoral student at Washington University School of Medicine, St. Louis, Missouri, told Infectious Disease Advisor.

Reference

Hasan SS, Miller A, Sapparapu G, et al. A human antibody against Zika virus crosslinks the E protein to prevent infection. Nat Commun. 2017;8:14722. doi: 10.1038/ncomms14722

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