Immunological study of deadly coronavirus in the Middle East offers hope of vaccine and treatment

April 30, 2014

About forty percent of the people who contract the newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) will die during the course of the infection.  Given the recent increase of diagnosed cases in the Middle East (which recently has surged above 400 cases) and the lack of vaccines and therapeutics, researchers are eager to discover new therapeutics that prevent virus entry into the cells, block replication and reduce morbidity and mortality.

A new study from Gillings School of Global Public Health, in collaboration with researchers at Harvard University, describes a novel panel of human monoclonal antibodies that bind to the virus and prevent infection.

Dr. Ralph Baric

Led by senior authors Ralph Baric, PhD, professor of epidemiology at the UNC Gillings School of Global Public Health and of microbiology and immunology in the UNC School of Medicine, and Wayne A. Marasco, MD, PhD, professor of medicine at Harvard Medical School and associate professor of cancer immunology and AIDS at Dana-Farber Cancer Institute, the study, “Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution,” was published online April 28 in  the Proceedings of the National Academy of Sciences (PNAS).

Some antibodies work by binding to the infected cell, thereby targeting the cell for destruction by white blood cells. Other neutralizing antibodies (nAb), however, defend the cell by binding to the virus and preventing virus infection.

“The human antibodies that we isolated were highly potent neutralizers of virus infectivity in the laboratory, and we are eagerly moving forward by testing these reagents in animal studies,” Baric said.

Study researchers identified seven human nABs that block MERS-CoV from attaching to lung primate cells. They identified three distinct regions on the surface Spike protein, within the Receptor Binding Domain (RBD), to which these antibodies bind and block entry into the target cells. Because the spike RBD binds the receptor for virus entry into cells, antibody binding blocks the ability of the virus to bind to its receptor, preventing infection. The scientists also identified mutations in the Spike protein that confer escape from these antibodies.

“Because antibodies bind to different locations in teh RBD, cocktails of two or more of these antibodies likely would prove highly efficacious in humans and animals,” said Sudhakar Agnihothram, PhD, research associate in the UNC Gillings School’s Department of Epidemiology and co-lead author on the paper. 

Altogether, these discoveries relate the first known report on human nAbs against MERS-CoV. The nAbs panel studied here offers much-needed hope for the development of a preventive therapy, especially for health-care workers, who have repeated exposures.

In addition to Baric, Marasco and Agnihothram, co-authors of the study are Rachel L. Graham, PhD, from Baric’s group in the Department of Microbiology and Immunology in the University of North Carolina School of Medicine; and Xian-Chun Tang (co-first author), Yongjun Jiao,  Jeremy Stanhope, Eric C. Peterson, Yuval Avnir, Jared Sheehan and Quan Zhu, from Marasco’s group at Harvard.