Chimeric attenuated dengue vaccines

Award Year 

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are viral diseases caused by one of four closely related viral serotypes and the most significant viral illnesses transmitted by mosquitoes to humans worldwide. Infec-tion with one of these serotypes provides immunity only to that specific serotype for life, so persons living in a dengue-endemic area can have more than one dengue infec-tion during their lifetime. Infections produce a spectrum of clinical illness ranging from a nonspecific (more) viral syndrome to severe and fa-tal hemorrhagic disease. Over 2.5 billion people, including travelers, are at risk of contracting dengue illness in such tropical regions of the world as South-east Asia, the Pacific Islands, the Caribbean, Mexico, Central America, South America, and parts of Africa. Each year tens of mil-lions of cases of DF occur and, depending on the year, up to hundreds of thousands of cases of DHF. The case-fatality rate of DHF in most countries is about 5%, but this can be reduced to less than 1% with proper treatment. Most fatal cases are among chil-dren and young adults. There is a critical worldwide public health need for a dengue vaccine that successfully immunizes and protects humans against all four types of dengue virus. The Centers for Disease Control and Preven-tion (CDC) have developed live-attenuated candidate vaccine viruses that share three identical genetic mutations responsible for the nonvirulent characteristics (attenuation determinants) of the vaccine viruses. The vaccine candidates have been genet-ically and phenotypically characterized in detail. Furthermore, new assays have been developed at CDC for the purpose of advancing the safety of these vaccine vi-ruses. Ultimately, these four strains will be combined to create a tetravalent vaccine to protect against all dengue disease with only one vaccine formulation.The CDC has licensed and transferred this vaccine technology to Inviragen, Inc., a small biotechnology company located in Fort Collins, Colorado. This technology trans-fer has moved these vaccine candidates to a commercial setting, where they can be manufactured under the controlled condi-tions required for product testing in humans. Success of the program will provide a safe, effective, low-cost, and easy-to-use tetrava-lent dengue vaccine that will save millions of lives and decrease the tremendous eco-nomic burdens caused by dengue disease. (less)