NOVEL ANTIBODY NEUTRALIZES RABIES VIRUS

Findings may lead to a lower cost, easily produced biologic for people exposed to rabies

June 15, 2005

Jamaica Plain, MA and Atlanta GA— A team of scientists at the Massachusetts Biologic Laboratories (MBL) of the University of Massachusetts Medical School (UMMS) and the U.S. Centers for Disease Control and Prevention (CDC) have developed a new substance, a novel human monoclonal antibody (MAB), which can neutralize multiple variants of rabies virus. The findings may lead to a more cost effective, easier to produce biologic that can be given to people who are bitten by rabid or potentially rabid animals. “Rabies continues to be a major public health problem around the world, so we were pleased to join with the CDC to search for a better and more accessible product for people who are exposed to this disease,” said Donna Ambrosino, MD, director of the MBL and a professor of pediatrics at the Medical School.

Details of the new antibody and the results of tests with the rabies viruses will be presented June 17 in Kiev, Ukraine at the “Rabies in Europe” conference, jointly organized by the World Health Organization (WHO), the Office International des Epizooties (OIE) based in Paris and the European Union (EU). “Modern biotechnology, as used to produce this antibody, will be a critical facet of effective rabies prophylaxis inthe future,” said Charles Rupprecht, VMD, MS, PhD, head of the rabies unit within the Division of Viral and Rickettsial Diseases at CDC.M

While deaths from rabies in the United States are relatively rare, over 40,000 people in the US are exposed to the disease each year and require post-exposure prophylaxis (PEP). Worldwide, however, rabies remains a significant problem, with health officials estimating that between six and 10 million people are exposed to rabid animals each year, resulting in some 40,000 to 70,000 deaths.

By using vaccine and human rabies immune globulin (hRIG) during PEP, patients are protected against rabies.The hRIG, which is derived from human blood, is an expensive material and is often in short supply in developing countries. To compensate, equine immune globulin derived from horse serum is used in many parts of the world, but it may carry significant side effects and is not an optimal product. To address the supply and side effect issues, work at MBL and the CDC has focused on developing MABs that could be used in place of hRIG. The effort used, in part, Medarex, Inc.’s ( Princeton, N.J.) UltiMAb Human Antibody Development System®, which uses transgenic mice to produce fully human antibodies. Researches at MBL vaccinated the mice with rabies virus then studied the animals’ immune responses, searching for antibodies that would recognize and bind to the rabies virus coat or glycoprotein. The team isolated a series of those antibodies, and tested them against live rabies virus strains in culture.

After painstaking work analyzing a host of antibodies, the team found one in particular that recognized and neutralized rabies viruses. That one antibody, called;HuMAB 17 C7, was tested against 25 different rabies viruses, representing major types known to affect animals around the world. In each case,HuMAB 17 C7 neutralized the rabies viruses in culture. To further test the antibody, the team conducted tests on laboratory rodents thatwere exposed to the live virus, then given human rabies vaccine both with, and without, the new HuMAB 17 C 7. In both cases, the procedure with the MAB protected the animals from developing the fatal disease.

Monoclonal antibodies can be produced in large quantities, at much lower costs than blood products. Also, MABs can be stock-piled in liquid form, or freeze-dried, so they are easier to distribute to remote sites. And since MABs are not derived from serum, they have none of the safety issues associated with typical human blood products. Thus, researchers are hopeful the novel HuMAB 17 C7 may become an effective alternative to hRIG.

Looking towards the future, the team at MBL and CDC are reviewing the public health issues, and evaluating potential collaborations to prepare for a phase 1 clinical trial to test the safety and tolerance of the HuMAB 17 C7 in otherwise healthy people.

 About the CDC

The Centers for Disease Control and Prevention is one of the 13 major operating components of theDepartment of Health and Human Services (HHS),which is the principal agency in the United States government for protecting the health and safety of all Americans and for providing essential human services, especially for those people who are least able to help themselves. Since it was founded in 1946 to help control malaria, CDC has remained at the forefront of public health efforts to prevent and control infectious and chronic diseases, injuries, workplace hazards, disabilities and environmental health threats.

About the Massachusetts Biologic Laboratories

The Massachusetts Biologic Laboratories is the only non-profit FDA-licensed manufacturer of vaccines and other biologic products in the United States. The laboratory was established in 1894; since then, the MBL's mission has been to improve public health through applied research, development and production of biologic products. MBL has been a part of the UMass Medical School since 1997.

About UMass Medical School

The University of Massachusetts Medical School is one of the fastest growing academic health centers in the country and has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $173 million in extramural research funding annually, 80 percent of which comes from federal funding sources. Research dollars enable UMMS scientists to explore human disease from the molecular level to large-scale clinical trials. Basic and clinical research leads to new approaches for diagnosis, treatment and prevention of disease. Visit www.umassmed.edu for additional information.

Contact: Michael Cohen,508-856-2000,Michael.Cohen@umassmed.edu