FDA scientists study monoclonal antibody that protects mice against a broad range of polioviruses

The results of a study in transgenic mice by scientists at the U.S. Food and Drug Administration (FDA) suggest that hybrid human/chimpanzee monoclonal antibodies (mAb) that were previously isolated in collaboration with the National Institutes of Health could be used in combination with drugs, a vaccine, or both, to improve their efficacy against polioviruses.

The worldwide campaign to stop the transmission of wild polioviruses may soon eliminate all sources of pathogenic virus except for an insufficiently characterized group of immunodeficient patients incapable of resolving poliovirus infection. They are not only at significant risk of developing paralysis, but are also a source of virulent polioviruses that could restart virus circulation. No effective treatment is known that would help the patients to clear the infection, and therefore the search for new antiviral strategies is underway.

The results of the FDA study showed that a specific antibody called mAb A12 neutralized a broad range of type 1 and type 2 polioviruses, as well as vaccine-derived poliovirus. The antibody also protected susceptible mice against lethal doses of the poliovirus when they received it before being exposed to the virus by intramuscular injection. mAb A12 also prevented paralysis of some mice that were treated hours after exposure to the virus.

The A12 antibody did not interfere with the ability of poliovirus to stimulate the immune system of vaccinated mice from developing antibodies that neutralized the virus. This suggests that treatment with antibody A12 in combination with polio vaccine might prevent development of polio symptoms until the immune system responds to either the vaccine or to contact with the wild poliovirus itself. The scientists also showed that that mAb A12 can neutralize poliovirus strains that are resistant to the investigational anti-poliovirus drug, V-073. Further study is needed, but this suggests that the antibody could be used to supplement antiviral therapy and prevent emergence of drug-resistant viruses.

The FDA scientists suggested that the antibody could be used to treat chronically infected individuals to have them stop shedding the virus, and for emergency post-exposure prophylaxis; they are currently working on testing this hypothesis.

The findings of this study provide support for initiating clinical evaluations in people of antibodies like mAb A12 in the treatment and prevention of polio.

TITLE
A single chimpanzee-human neutralizing monoclonal antibody provides post-exposure protection against type 1 and type 2 polioviruses
Journal of Clinical Virology 65 (2015) 32-37
HTTP://dx.doi.org/10.1016/j.jcv.2015.01.023

AUTHORS

Diana Kouiavskaiaa, Zhaochun Chenb, Eugenia Dragunskya, Olga Mirochnitchenkoa,

Robert Purcellb, Konstantin Chumakova,∗

a Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 52, Room 1126, Silver Spring,

MD 20993-0002, USA

b National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA