The Massachusetts Biologic Laboratories (MBL) of the University of Massachusetts Medical School (UMMS) and the Serum Institute of India today announce the formation of an historic collaboration to bring to the world a new, more cost-effective approach for preventing rabies in people.
The institutions will collaborate to test and manufacture a new monoclonal antibody (MAB) created by scientists at the MBL, in conjunction with the U.S. Centers for Disease Control and Prevention (CDC), which can neutralize multiple variants of the rabies virus. The MBL and Serum Institute plan to launch a Phase 1 clinical trial in India in 2007 to assess the safety and tolerability of the new MAB in people, with hopes of having the new, lower-cost treatment available within two years for people exposed to rabies. The treatment would then be made broadly available in India shortly thereafter.
"Rabies is a major global public health problem, so we are very pleased to be partnering with Serum Institute to bring this new approach to the millions of people who need it each year," said Donna Ambrosino, MD, director of the MBL and a professor of pediatrics at the Medical School. "The institute's top level scientific resources, its commitment to public health, and its global reach, make it the best partner for us in this important initiative."
Based in Pune, India, the Serum Institute is the world's largest manufacturer of vaccines. The Institute's specific mission is to bring cost-effective vaccines and biologics to the developing world. Today, half of all children inoculated in the world receive vaccines from the Serum Institute. Cyrus S. Poonawalla, PhD, chairman of the Serum Institute, was recently awarded the prestigious Sabin Vaccine Institute Award, in recognition of his institute's efforts over the past 35 years to improve and protect people's health, particularly children. "The underprivileged should have an equal opportunity to utilize modern science," Dr. Poonawalla said. "This new partnership, I believe, will eventually bring relief to many people around the world."
While deaths from rabies in the United States are rare, more than 40,000 people in the U.S. are exposed to the disease each year and require post-exposure prophylaxis (PEP). Worldwide, however, rabies remains a major public health problem. The World Health Organization estimates that at least 10 million people are exposed to rabid animals each year, resulting in some 55,000 deaths.
The rabies virus infection causes acute encephalitis that is fatal once symptoms appear; however, the infection is preventable by prompt treatment following exposure. By using a rabies vaccine and human rabies immune globulin (hRIG) during treatment, patients are protected from the fatal disease. The hRIG, which is derived from human blood, is an expensive material and is often not available in developing countries. To compensate, equine immune globulin derived from horse serum is used in many parts of the world, but it can carry significant side effects and is not an optimal product.
To address the supply problems and side-effect issues, the CDC and MBL launched an effort to find a MAB that could be used in place of hRIG. The work used, in part, the HuMab mice« from Medarex, Inc. (Princeton, N.J.) which uses transgenic mice to produce fully human antibodies. Researches at MBL vaccinated transgenic mice with the rabies virus and 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. That research found one MAB in particular, now called HuMAB 17 C7, which worked dramatically and broadly. It was tested against 25 different rabies viruses, representing the major types known to affect animals, and in each case neutralized the rabies viruses in culture. The antibody was then tested in a rodent model of disease, using rabies vaccine and the HuMAB 17 C7, which fully protected the animals from developing the fatal disease.
Furthermore, monoclonal antibodies can be produced in large quantities, at much lower costs than blood products and can be stockpiled 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.
As part of the collaboration agreement, scientists from the MBL will work with their counterparts in India to help the Serum Institute build its own internal MAB production facility, thereby bringing this leading-edge biologics technology to India for the first time. Serum Institute already produces much of the rabies vaccine used in India and now with the new technology of MAB will be positioned to deliver full protection to exposed individuals. The new MAB will be studied jointly under US FDA and Indian FDA regulations resulting in eventual world-wide distribution. "The Serum Institute feels this is a unique opportunity to use cutting-edge technology for saving lives across the globe," Dr. Poonawalla said.
To formalize the collaboration agreement, and to continue the planning for the clinical trial and manufacturing process, a delegation from the MBL and Medical School traveled to India last month. "It is our hope this collaboration around rabies will be the first of many joint initiatives with the Serum Institute," Dr. Ambrosino said. "This is an exciting partnership, one that I believe holds out hope to address many serious public health problems in the world today."