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9. Development of Monoclonal Antibodies against SARS-associated Coronavirus: Specific Targeting for Early Diagnosis and Future Treatment (WITHDRAWN)
 
Funds : Research Fund for the Control of Infectious Diseases (investigator-initiated projects)
Project Status : Closed
Reference No. : 01030322
Project Title : Development of Monoclonal Antibodies against SARS-associated Coronavirus: Specific Targeting for Early Diagnosis and Future Treatment (WITHDRAWN)
Applicant(s) : Lai KN(1)
Kwong YL(1)
Chung SMS(2)
Affiliation(s) : Department of Medicine, The University of Hong Kong(1)

Institute of Molecular Biology, The University of Hong Kong

Approved Amount (HK$) : $805,000.00
Abstract : Severe acute respiratory syndrome (SARS) is a new emerging disease that has affected many countries, with more than 8,000 cases reported. This new infection affects Hong Kong significantly with over 1700 cases in late May and mortality exceeding 260 since the first occurrence of the infection in late February 2003. A novel virus, the SARS-associated coronavirus (CoV), has been identified as the causal agent. Current strategy of initial detection of coronavirus infection relies on the use of reverse transcription polymerase chain reaction (RT-PCR). Although RT-PCR is highly sensitive, there are a number of pre-analytical problems that are limiting. Firstly, a suitable specimen containing the virus, such as nasopharyngeal aspirate, needs to be procured. During the procedure, considerable risks to health care workers arise. Secondly, handling of a highly infectious material is problematic. Thirdly, labile RNA may undergo degradation, thus giving false negative results. Serologic diagnosis is more robust. It is less sensitive in the initial phase of the disorder, because antibody production against the virus usually does not occur before the first week. However, it is a more reliable test after the second week of infection, and from an epidemiological standpoint, a more useful investigative tool. Nevertheless, serologic confirmation of the infection that takes 3 weeks is usually late for commencement of treatment and delayed treatment can be fatal. Furthermore, much is still undefined about the serologic diagnosis of SARS. This is largely owing to the lack of knowledge of what antigenic determinants in the coronavirus are recognized by the host immunity. Similar to other viral infections, some antigenic determinants may give rise to antibodies that are useful for diagnosis. Other antigenic determinants may lead to the formation of antibodies that are protective against viral entry or replication. Therefore, the definition of the types of antigenic determinants and the functions of their respective antibodies is potentially useful for both diagnosis of the disease and its treatment. In this project, we propose to express the coronaviral proteins in vitro. B lymphocytes from patients with immunity to the coronavirus will be used to produce specific antibodies against coronaviral antigens. These monoclonal antibodies will be of tremendous value in providing a safe and rapid serum and tissue diagnosis of SARS-related coronavirus infection. Therapeutic potentials are also possible for these antibodies as an adjuvant immuno-modulatory therapy.
Keywords : Severe acute respiratory syndrome, coronavirus, B lymphocytes, monoclonal antibody, diagnosis, adjuvant therapy, human
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Last revision date: 15 August 2006