Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS

By Frank Blanchard, Staff Writer
Rabbit lung

A section of rabbit lung following MERS-CoV infection containing two small airways (bronchioles), bronchus-associated lymphoid tissue, and a small blood vessel. Distributed within the areas directly surrounding both airways and the vessel are an abundance of inflammatory cells, largely composed of eosinophils with fewer histiocytes and lymphocytes. These cells can also be observed in the lumen of the blood vessel. The alveolar spaces contain variable numbers of alveolar macrophages. Image from the The Journal of Infectious Diseases, provided courtesy of Katherine Houser, Laboratory of Infectious Diseases, NIAID.

A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research.

MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

To address the need, a research team from the National Institute of Allergy and Infectious Diseases (NIAID) and NCI characterized a human monoclonal antibody, m336, which has the ability to attach itself to the MERS virus in a way that renders the virus harmless. The group conducted a series of experiments to see if the antibody would protect laboratory animals from the disease, and the results were recently published in The Journal of Infectious Diseases.

Antibodies were given to a group of rabbits using two methods, intravenously and intra-nasally, and were administered one day before being exposed to the MERS virus. A second group of the lab animals received a placebo.

One day after infection, the animals that received the antibodies showed an immediate drop in the amount of virus, and after three days, they had a more than 500-fold reduction in virus compared to the control group, the researchers reported. Those animals given the antibody showed no evidence of inflammation or illness after three days, while the unprotected group showed early symptoms of the disease.

The researchers also assessed the effectiveness of giving the antibody as a treatment following infection, but it was not effective when administered after exposure to the virus.

“These results indicate the m336 antibody administered prior to exposure is able to prevent MERS-CoV infection and warrants further development as a medical countermeasure against MERS-CoV infection,” the researchers reported.

The research group included corresponding author Kanta Subbarao, chief of the Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, NIAID; Dimiter Dimitrov, Ph.D., head of the Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research at NCI at Frederick; and their colleagues at NIH and NIAID.