GREG KELLER AP Business Writer NEUVILLE-SUR-SAONE, France (AP) — Sanofi-Aventis SA began work Tuesday on a €350 million ($477 million) plant that is to be devoted to production of the world's first vaccine against dengue fever, a public health threat for some two-fifths of the worlds population. The company says its vaccine plant in this town north of the French city of Lyon is the largest single industrial investment it has ever made. By 2013 it is hoped the plant will begin turning out a dengue vaccine that the company is currently testing. Dengue is a potentially lethal mosquito-borne infection whose spread has grown dramatically in recent decades, according to the World Health Organization. There is currently no available vaccine The WHO estimates that there are around 50 million dengue infections worldwide every year, making it second only to malaria among tropical diseases. Sanofi-Aventis cited other research that puts the total infections as high as 230 million annually. About two-fifths of the world's population lives in areas where the disease is widespread. Sufferers experience a range of symptoms, from mild fever to incapacitating high fever with severe headaches, pain behind the eyes, muscle and joint pain and rash, according to the WHO. Sanofi-Aventis Chief Executive Chris Viehbacher said sales of the vaccine could reach €1 billion annually. "Its hard to give a precise estimate, but I wouldn't be investing €350 million euros if there wasn't a strong chance that this is the biggest vaccine ever," Viehbacher said. Sanofi-Pasteur, the world's largest vaccine maker, began working on a vaccine against dengue in the early 1990s, and has already spent "hundreds of millions of euros" in research and development on the treatment, Viehbacher said. Dengue fever is caused by four different viruses, which has complicated scientists' hunt for a vaccine. Southeast Asia and the Western Pacific are the regions worst affected by dengue fever, according the the WHO. The mosquito that transmits the virus is particularly well adapted to urban environments, giving it the potential to become "a major public health problem of the future," said Dr. Elias Zerhouni, Sanofi-Aventis' science and technology advisor. Sanofi-Aventis said last month it plans to widen Asian clinical trials of a potential first-ever dengue fever vaccine. The drug company's vaccine division, Sanofi Pasteur, said last month it will test the vaccine in Singapore and Vietnam, adding to ongoing studies in Thailand and the Philippines. The company said it may seek regulatory approval of the vaccine as early as 2012, Sanofi-Aventis spokesman Jean-Marc Podvin said. The Asian trials are part of a second phase of studies that includes tests on children and adolescents in Peru and Mexico, Melanie Saville, head of Sanofi's dengue program, said in a statement. A third and final phase would involve large-scale trials and production of the drug, Saville said. Sanofi Pasteur's new plant in Neuville-sur-Saone, 20 miles north of Lyon, is Sanofi's 11th vaccine production plant in the world. The company has invested about 1.5 billion euros in new vaccine production capacity over the last five years. Sanofi Pasteur had sales last year of 2.9 billion euros and employs 11,000 people at 10 vaccine production and R&D sites in France, the U.S., Canada, Argentina, China and Thailand. Earlier this month Sanofi received US FDA licensing for a new flu vaccine plant in Swiftwater, Pennyslvania. The plant, which cost $150 million to build, will have a capacity of 100 million doses, bringing Sanofi's total U.S. vaccine production capacity to 150 million doses.