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Hunting a chikungunya vaccine

French scientists begin safety testing of vaccine to quell ever-growing outbreak of the mosquito virus

By | January 16, 2007

As the Indian Ocean region continues to grapple with the largest recorded outbreak of the mosquito virus chikungunya, scientists in France have started laboratory safety testing of a chikungunya vaccine developed and abandoned years ago by the U.S. Army, then recently passed on to the French. If no prions or other contaminants are found in the U.S. vaccine, French scientists plan clinical trials next fall, according to Antoine Flahault, head of France's Chikungunya Research Task Force and director of France's new School of Public Health (Ecole des Hautes Etudes en Sante Publique). The first study would start in France next September in 100 Parisian hospital workers, followed two months later by a study of 500 volunteers in Reunion, a French island near Madagascar where a third of the population has been infected (266,000 cases, 250 deaths). A study in macaque monkeys, native to nearby Mauritius, is also planned. Although vaccine development is notoriously fickle, "using the U.S. vaccine will save us five years," Flahault told The Scientist, adding that Sanofi Pasteur plans to produce the vaccine commercially. "The Americans were very lucky to discover a promising vaccine strain... If all goes well, the commercial vaccine will be available in five years." Chikungunya was until recently a little-known mosquito-borne alphavirus that causes few deaths but leads to debilitating joint pain, fever and arthritic symptoms. Isolated in 1953 in Tanzania, the virus sparked sporadic epidemics in Africa and Asia. The latest outbreak has been traced to a viral strain that surfaced in Kenya in 2004, spread to the Comoros and Reunion in 2005 and 2006, and has the same genomic sequence as the virus that has caused 1.5 million cases in India, said Flahault. In the late seventies, U.S. Army scientists at the Walter Reed Army Institute of Research and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) started developing the only known chikungunya vaccine tested on humans, a live attenuated vaccine created from an isolate taken from a patient in Thailand. The research stopped in 1997 despite promising phase II study results (57 out of 58 evaluable vaccinees developed a neutralizing antibody by day 28, and 85% were seropositive a year later) due to lack of a commercial partner, changing budget priorities, and "difficulty envisioning how final field efficacy trials would be conducted due to the unpredictable nature of chikungunya outbreaks," said Col. David Vaughn, outgoing director of the Military Infectious Diseases Research Program at the U.S. Army Medical Research and Materiel Command in Fort Detrick, Maryland. "Chikungunya tends to have fairly explosive outbreaks, but only every few years, so it's a more unpredictable market than other tropical diseases," Vaughn told The Scientist. "But if we had a million cases as they do in India...we'd be focusing on it." So far, the CDC has identified 40 or 50 cases imported to the U.S. by travelers to India, said molecular virologist Ann Powers, Chief of the Alphavirus Laboratory with the CDC's Division of Vector-Borne Infectious Diseases in Fort Collins. In September, 2006, the U.S. Embassy in Paris announced a U.S. Government agreement to transfer research records, vaccine supplies, and seed stocks so the French could resume vaccine development. The cooperative deal involves a partnership between the U.S. Military and other agencies, the French Ministry of Health, INSERM, and the Institut Pasteur. Flahault said that he did not believe the two countries had struck a commercial agreement. Vaughn, meanwhile, said if the vaccine proves effective, "a licensure agreement between USAMRIID and a commercial manufacturer will be needed." Because it was grown in cells fed calf serum, the U.S. vaccine is being tested for the prions that cause bovine spongiform encephalopathy, Flahault said. The epidemic also sparked interest in India, where scientists are reportedly also working on a chikungunya vaccine. Indian scientists did not respond to requests for comment. Clare Kittredge ckittredge@the-scientist.com Links within this article: CDC Outbreak Notice Update: "Chikungunya Fever: India and Indian Ocean Islands," released April 21, 2006, last updated Oct. 24, 2006 http://www.cdc.gov/travel/other/2006/chikungunya_india.htm C. Kittredge, "Mosquito virus spreading," The Scientist, Feb. 24, 2006 http://www.the-scientist.com/news/display/23145 Antoine Flahault, recent publications listed in PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_AbstractPlus&term=%22Flahault+A%22%5BAuthor%5D Paul Reiter et al, "Aedes albopictus as an epidemic vector of chikungunya virus: another emerging problem?" The Lancet, August, 2006 http://courses.washington.edu/pabio550/readings06/Emerging%20Chikungunya.pdf Isabelle Schuffenecker et al, "Genome Microevolution of Chikungunya Viruses Causing the Indian Ocean Outbreak," PLoS MEDICINE, July, 2006 'http://www.plos.org/press/plme-03-07-brisse.pdf Christophe Paquet et al, "Chikungunya Disease Outbreak, Reunion Island," CDC Emerging Infectious Diseases, December, 2006 http://www.cdc.gov/ncidod/EID/vol12no12/06-0710.htm U.S. Embassy, Paris, press release, "US-France Cooperation On Chikungunya Vaccine," Sept. 14, 2006 http://www.amb-usa.fr/texts/chikungunya.pdf World Heath Organization, "Chikungunya Fever, a re-emerging Disease in Asia" http://www.searo.who.int/en/Section10/Section2246.htm V. Narayanan, "Private lab files patent for chikungunya vaccine," News Today, Oct. 25, 2006 http://newstodaynet.com/25oct/ss7.htm
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