Immunoprevention and imunotherapy of SARS infection
The 114-day long epidemic wave of Severe Acute Respiratory Syndrome (SARS) swept 29 countries, sickened a reported 8 096 people, left 774 patients dead in its wake, and almost completely paralysed Asia's economy. Aggressive quarantine measures and rising summer temperatures successfully terminated the first eruption of SARS and provided at least a temporal break, allowing scientists to consolidate what they have learned so far and plan for the future.
The SARSVAC project proposal was prepared in response to urgent medical and societal needs for immunopreventive (vaccination) and immunotherapeutic measures for SARS. An integrated strategy for developing effective vaccines and for establishing effective therapeutic treatment will be developed. The strategy for vaccine development will follow two parallel approaches: (1) the preparation of a classical inactivated vaccine (as already done for other Coronaviruses); and (2) the definition of potential antigens and T/B protective epitopes through the study of SARS-CoV derived virus-like particles (VLPs), pivotal to the understanding of SARS-CoV morphogenesis and virion maturation.
The immunotherapeutic strategy will rely on the development and validation of neutralising human antibodies to SARS-CoV. Under this project, academia experts in immunology, vaccinology, and molecular biology have joined forces with industrial vaccine production experts, in order to develop preventive and therapeutic measures for SARS.[+] Read More
The evolution and spread of the etiological agent of SARS, a novel Coronavirus, has resulted in an unparalleled international effort coordinated by the World Health Organization (WHO) to characterise the virus, develop diagnostic tests, and formulate optimal treatment protocols to reduce morbidity and mortality. The SARS Coronavirus is believed to have jumped over from an animal host to people in Guangdong province, southern China, in November 2002 and then to have spread rapidly throughout the world via air travel. Following unprecedented collaboration between laboratories worldwide, the virus could be isolated and its sequence was published in April 2003.
The association of the virus with the disease was confirmed when macaques that were inoculated with the virus developed symptoms similar to those observed in human cases of SARS. When the epidemic finally waned, WHO counted a cumulative number of 8 096 probable SARS cases and 774 deaths in a geographical area spanning 29 countries. Economists have estimated that the overall cost of the outbreak may approach USD 100 billion - mostly as a result of cancelled travel and decreased investment in the affected region.
SARS is mainly characterised by flu-like symptoms including high fever, headache, chills, rigors, dizziness, myalgia, sputum production, sore throat, coryza, nausea, vomiting and diarrhoea. The incubation period is at least 2 days but no longer than 10 days. The overall mortality rate was about 10%, but varied profoundly with age; although SARS affected relatively few children and generally appeared to be milder in the paediatric group, the mortality rate in the elderly was as high as 50%. Any pre-existing lung ailment complicates the disease, and conditions such as emphysema are more common in the elderly. Although it is now well established that the SARS virus can kill on its own, other co-infection with different pathogens can exacerbate the illness.
While SARS did not re-emerge in the human population in 2004, most likely the virus is still circulating in an unknown animal reservoir, making the development of preventive and therapeutic strategies against it a pressing need.
The Novartis Research Group in Siena (Italy) promptly reacted to the global emergency and was among the first to isolate the virus and sequence its genome. Two other research groups started to collaborate with Novartis, i.e. the Institute of Virology at the University of Marburg (Germany), to provide expertise in virology, and the Istituto di Ricerche Biomediche in Bellinzona (Switzerland), to provide expertise in the production of human monoclonal antibodies against the SARS Coronavirus.
Building on this previous experience, a research project is proposed targeting three main objectives:
The results of this project could be measured for points 1 and 2 (above) as:
The project has already concluded, with the following final results:
Results obtained within the scope of the project will be enhanced by two factors. The first is the further development of SARS vaccines by partner 1 (Novartis) which will comprise clinical testing of the vaccine. This will guarantee that the seed money of the EU Commission will serve to promote important applications and products. Along the same line, the therapeutic monoclonal antibodies will be industrialised for process development.
This result could also become an applied tool first, and probably a product within the strategies proposed by the EU Commission in FP6. On the whole, the scientific outcomes of this project are expected to have a very high potential impact reinforcing the competitiveness of the European researcher in the vaccine field.