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Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. The present invention is directed toward vector stage replication-defective flaviviruses that are replication-defective in mosquito vectors that transmit them to humans. The replication-defective flaviviruses of the present invention demonstrate a limited ability to replicate in the vector organisms that transmit flaviviruses from one host to another.

The current invention provides a nucleic acid sequence comprising the genome of infectious hepatitis C viruses (HCV) of genotype 2a. The encoded polyprotein differs from those of the infectious clones of genotypes 1a and 1b (U.S. Patent 6,153,421) by approximately thirty (30) percent. It covers the use of this sequence and polypeptides encoded by all or part of the sequence, in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV. Additional information can be found in Yanagi et al.

The current invention provides nucleic acid sequences comprising the genomes of infectious GB virus B, the most closely related member of the Flaviviridae to hepatitis C virus (HCV). It also covers chimeric GBVB-HCV sequences and polypeptides for use in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV. Additional information can be found in Bukh et al. (1999), Virology 262, 470-478.

The current invention provides nucleic acid sequences comprising chimeric viral genome of hepatitis C Virus (HCV) and bovine viral diarrhea viruses (BVDV). The chimeric viruses are produced by replacing the structural region or a structural gene of an infectious BVDV clone with the corresponding region or gene of an infectious HCV. It covers the use of these sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV.

This invention is based on the discovery of the swine hepatitis E virus (swine HEV), the first animal strain of HEV identified and characterized, and its ability to infect across species. The inventors have found that the swine HEV is widespread in the general pig population in the United States and other countries and that swine HEV can infect non-human primates. The inventors have amplified and sequenced the complete genome of swine HEV. The capsid gene (ORF2) of swine HEV has been cloned and expressed in a baculovirus expression system.

Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. This invention relates to dengue virus mutations that may contribute to the development of improved dengue vaccines. Site directed and random mutagenesis techniques were used to introduce mutations into the dengue virus genome and to assemble a collection of useful mutations for incorporation in recombinant live attenuated dengue virus vaccines.

Hepatitis E is endemic in many countries throughout the developing world, in particular on the continents of Africa and Asia. The disease generally affects young adults and has a very high mortality rate, up to 20%, in pregnant women. This invention relates to the identification of a neutralization site of hepatitis E virus (HEV) and neutralizing antibodies that react with it. The neutralization site is located on a polypeptide from the ORF2 gene (capsid gene) of HEV.

Hearing loss is a common communication disorder affecting nearly 1 in 1,000 children in the United States alone, and nearly 50% of adults by the age of eighty. Hearing loss can be caused by environmental and disease-related factors; however, hearing loss due to genetic factors accounts for approximately 50% of cases.

This invention claims antibodies and/or fragments thereof specific for hepatitis A virus (HAV) and the use of the antibodies in the diagnosis, prevention, and treatment of hepatitis A. Hepatitis A is the most common type of hepatitis reported in the United States, which reports an estimated 134,000 cases annually, and infects at least 1.4 million people worldwide each year. HAV is a positive sense RNA virus that is transmitted via the fecal-oral route, mainly through contaminated water supplies and food sources.

This invention describes a method for vaccination against Ebola virus. Outbreaks of hemorrhagic fever caused by the Ebola virus, particularly the Zaire subtype, are associated with high mortality rates. The virus is very contagious, and during an outbreak, presents a threat to anybody who comes into contact with an infected person. Because the virus progresses so rapidly and the mortality rate is so high, there is little opportunity to develop natural immunity, making vaccination a promising intervention.