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WORCESTER, Mass. and PRINCETON, N.J. -- Presenting last Saturday at the annual meeting of the Infectious Disease Society of America, a team of scientists from the Massachusetts Biologic Laboratories (MBL) of the University of Massachusetts Medical School (UMMS) in Jamaica Plain and at the Medical School's Worcester campus, in partnership with researchers at Medarex, Inc. announced they have neutralized the SARS virus in non-human tissue cultures.
The breakthrough was accomplished using antibodies from genetically engineered mice immunized with a protein the SARS virus uses to infect cells. Researchers believe this advance may lead to treatments to prevent infection with SARS after individuals have been exposed to the virus, and potentially to therapeutic products to treat those already infected. This important progress comes just six months after the Centers for Disease Control and Prevention (CDC) provided the SARS virus to UMMS to launch this research.
"We believe this is a very important and very exciting breakthrough," said Donna Ambrosino, MD, director of the MBL and a professor of pediatrics at the Medical School. "We've got mice producing the right antibody, so we hope it's only a matter of time before we isolate the one cell that will become the basis for a monoclonal antibody to prevent SARS in individuals exposed to the illness."
The advance came from MBL's success in producing a protein from the SARS virus that results in attachment and entry into cells. If that protein, or portions of the protein, could be blocked, it is believed that the virus would not be able to infect the host. To test the theory, the protein was introduced in specialized mice developed by Medarex that produce fully human antibodies when immunized. After immunization with the protein, the mice responded with human antibodies that bind to the protein. Sera from those mice were taken and tested against the live SARS virus in tissue culture. The antibodies in the sera neutralized the virus's ability to infect cells in the culture.
The SARS work at MBL was led by William Thomas, PhD, and the team at the Medical School's Worcester campus includes Thomas Greenough, MD, Katherine Ruiz de Luzuriaga, MD, Robert Finberg, MD and John Sullivan, MD. The team at Medarex includes Israel Lowy, MD, PhD, Robert Graziano, PhD and Nils Lonberg, PhD.
"We are extremely pleased with the progress that has resulted from the collaborative efforts of the scientists at MBL, UMass Medical School and Medarex," said Donald L. Drakeman, president and CEO of Medarex, Inc. "In addition, we are very appreciative of the ongoing relationships between MBL and NIH (National Institutes of Health) and CDC, which have proven beneficial to our research."
The next step in this research is to isolate the individual cell from the mice that produces the neutralizing antibody to the SARS virus. There are many cells that could be producing the right antibody and researchers at the MBL are now at work isolating cells and testing their efficacy against the SARS virus. The researchers believe that eventually the key cell will be found, cloned and a monoclonal antibody will be produced from that cell. "We hope to have a candidate cell line soon," Ambrosino said. "If all goes well, there is a chance we could have something ready for testing in people over the next two years."
"This productive collaboration is a good example of a private and public sector partnership to meet an urgent medical need posed by a newly emergent infectious disease," said Israel Lowy, MD, PhD, director of infectious diseases at Medarex, Inc. "We believe that human monoclonal antibodies may prove to be potent therapeutic agents in a variety of infectious diseases."
SARS is a viral respiratory illness caused by a coronavirus. SARS was first reported in Asia in February 2003, and over the next few months, the illness spread to more than two dozen countries in North America, South America, Europe, and Asia. According to the World Health Organization, during the SARS outbreak of 2003, a total of 8,098 people worldwide became sick with SARS; of these, 774 died. The SARS global outbreak of 2003 was contained; however, it is expected that the disease could re-emerge in an annual cycle similar to the common flu.
"We believe that both the world health community's response to the outbreak of SARS, and the pace of progress in our efforts at the Medical School, have been outstanding," said Sullivan, director of the office of research at UMass Medical School. "Research is a painstaking process, yet in this case, things fell into place quickly. The combination of the expertise at the MBL, the ability to work with the live virus at our containment facility in Worcester, NIH support, and our partnership with Medarex that gave us access to their important technology, all made this rapid advance possible."
Source: Medarex, Inc.