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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.

Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection. This invention claims nine major salivary proteins from the sand fly vector of Leishmania major, Phlebotomus papatasi, nucleic acids encoding the proteins, vaccines comprising the proteins and/or nucleic acids, and methods of producing an immune response to prevent Leshmaniasis.

Purines such as adenosine and ATP have been shown to play a wide array of roles in biological systems such as inter alia, modulator of vasodilation and hypotension, muscle relaxant, central depressant, inhibitor of platelet aggregation, regulator of energy supply/demand, responder to oxygen availability, neurotransmitter and neuromodulator. All P1 and P2 receptor nucleoside ligands suffer from chemical instability that is caused by the labile glycosidic linkage in the sugar moiety of the nucleoside.

This invention relates to the use of several peptides from the salivary glands of various sand fly species for the control of leishmania infection. Many of these peptides were shown to be effective in eliciting potent immune responses in animal models and are excellent candidates for the development of vaccines against the disease. A vaccine comprising one of the peptides was used to protect mice challenged with parasites and salivary gland homogenates.

It is estimated that over 40 percent of the adult population in the United States has periodontal disease in one form or another. Periodontal Disease is a chronic infection of the periodontal ligament (PDL) and the adjacent bone and cementum. The effects of Periodontal Disease range from simple gum inflammation to, in extreme cases, tooth loss.