A team of researchers from Purdue University, Vanderbilt University Medical Center, and the University of Wisconsin have identified antibodies against the respiratory virus that can cause a rare polio-like illness that causes paralysis in children. The virus, enterovirus 68, has binding sites for the antibodies. Structural analysis of the virus shows that the antibody binding sites (shown here in gold and blue) do not overlap. Credit: Purdue University / Richard Kuhn
Researchers from Vanderbilt University Medical Center, Purdue University, and the University of Wisconsin-Madison have isolated human monoclonal antibodies that can potentially prevent a rare but devastating polio-like illness in children related to a respiratory viral infection.
The disease, called acute flaccid myelitis (AFM), causes sudden weakness in the arms and legs after a fever or respiratory illness. More than 600 cases have been identified since the US Centers for Disease Control and Prevention began tracking the disease in 2014.
There is no specific treatment for AFM, which tends to strike in late summer or early fall and has been associated with some deaths. However, the disease has recently been linked to a group of respiratory viruses called D68 enterovirus (EV-D68).
Researchers from the Vanderbilt Vaccine Center isolated antibody-producing blood cells from the blood of children who had previously been infected with EV-D68. By fusing blood cells with fast-growing myeloma cells, the researchers were able to generate a panel of monoclonal antibodies that potently neutralized the virus in laboratory studies.
Purdue’s colleagues determined the structure of the antibodies, which shed light on how they specifically recognize and bind EV-D68. One of the antibodies protected mice from respiratory and neurological diseases when administered before or after enterovirus infection.
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Maps of strain-specific neutralizing antibody EV68-159 (left) and broadly neutralizing antibody EV68-228 (right) bound to viral proteins in enterovirus D68. Credit: Vogt et al., Sci. Immunol 5, eaba4902 (2020)
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The “footprints” of where the body’s potent neutralizing antibodies (gold and blue) bind to antigen fragments in the enterovirus D68. Credit: Vogt et al., Sci. Immunol 5, eaba4902 (2020)
“We were excited to isolate potent human antibodies that inhibit this devastating polio-like virus, and these studies will form the basis for taking them into clinical trials,” said Dr. James Crowe, director of the Vanderbilt Vaccine Center; Ann Scott Carell President and Professor of Pediatrics and Pathology, Microbiology and Immunology at Vanderbilt University School of Medicine.
Binding sites of two highly neutralizing antibodies to D68 enteroviruses – highly reactive cross-reactive EV68-159 (gray) and EV68-228 (purple) – along the lines of symmetry in enterovirus D68. Viral proteins are blue, green, and red. Credit: Vogt et al., Sci. Immunol 5, eaba4902 (2020)
“Studying infectious diseases from a very basic level and applying the results to an animal model of disease is very powerful; hopefully, our studies will translate into a therapeutic future for this disease in children,” said Richard Kuhn, distinguished from Purdue Trent and Judith Anderson. Science teacher; Director of the Krenicki family, Purdue Institute for Inflammation, Immunology, and Infectious Diseases.
The study is published in Immunology science.
Antibodies Observe Mosquito-Borne Ross River Fever
MR Vogt el al., “Human Antibodies Neutralize Enterovirus D68 and Protect Against Infection and Paralytic Disease” Immunology science (2020). immunology.sciencemag.org/look … 6 / sciimmunol.aba4902
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