Compositions for protecting subjects from diseases caused by (+) SS RNA virus are described herein. The compositions include (i) a vector containing a DNA encoding a RNA molecule of an infectious (+) SS RNA virus operably linked to a eukaryotic RNA polymerase promoter and a carrier; or (ii) (+) SS RNA viruses obtained from eukaryotic cells transfected with the vector of (i) and a carrier.

A heterologous expression cassette, DNA construct and vaccine composition for immunization against flavivirus and/or other pathogens. DNA constructs, recombinant viruses and vaccine compositions containing the recombinant viruses were obtained. This invention also concerns and provide an improved expression vector of the live-attenuated yellow fever 17D virus. Modifications in the expression cassette of heterologous proteins in the intergenic E/NS1 region of the yellow fever 17D vaccine virus, were made. The two new functional domains inserted in the expression cassette were (1) a coding sequence for the N-glycosylation motif, located between the NS1 N-terminal motif and the heterologous protein and (2) a sequence which promoted the proteolytic cleavage, or not, of the recombinant protein in such a way as to release it from its C-terminal containing the transmembrane domains and, consequently, from its association with the membrane of the endoplasmatic reticulumER.

A group of mosquito-borne flaviviruses that cause fatal encephalitis in humans is among the most important of all emerging human pathogens of global significance. This group includes Japanese encephalitis virus (JEV), West Nile virus, St. Louis encephalitis virus, and Murray Valley encephalitis virus. In the present disclosure, the first reverse genetics system has been developed for SA14-14-2, a live JE vaccine that is most commonly used in most JE-endemic areas, by constructing an infectious bacterial artificial chromosome that contains the full-length SA14-14-2 cDNA. Using this infectious SA 14-14-2 cDNA, combined with a mouse model for JEV infection, a key viral neurovirulence factor has been discovered that is a conserved single amino acid in the ij hairpin adjacent to the fusion loop of the viral E glycoprotein, which regulates viral infectivity into neurons within the central nervous system.

The invention relates to a Zika viral vector vaccine comprising nucleic acid encoding a Zika virus structural antigen, wherein the nucleic acid encoding a Zika virus structural antigen comprises a sequence encoding Zika virus envelope DIII, or part thereof. The invention further relates to a Zika viral vector vaccine in combination with a Chikungunya viral vector vaccine.

Disclosed herein are compositions comprising one or more subgenomic Flavivirus RNA (sfRNA) elements and using those compositions in methods of improving mRNA transcript stability, improving mRNA transcript translation efficiency, enhancing gene therapy, and treating and/or preventing a disease or disorder.

Disclosed herein are nucleic acid constructs comprising a replication defective Zika virus vector and one or more coronavirus sequences and compositions thereof. The constructs relates to compositions and methods for inducing an immune response against coronavirus antigens due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak. The results herein indicate that these coronavirus constructs are safe and will induce an immune response that may provide protection against coronaviruses.

The present invention relates to attenuated, immunogenic West Nile virus chimeras built on a dengue virus backbone for the production of immunogenic, live, attenuated West Nile virus vaccines.

Replicon virus-like particles can be used as flavivirus vaccines.

Replicon virus-like particles can be used as flavivirus vaccines.

The invention provides, inter alia, improved replicons and vectors encoding them, where the replicons provide sustained expression of an encoded protein. These replicons comprise flavivirus replicases and heterologous protein coding sequences, wherein the heterologous protein coding sequences are flanked by separation sequences for improved efficacy. These nucleic acids provided by the invention, including self-replicating RNAs provided by the invention, are useful in methods of protein expression, such as for vaccines (e.g., for methods of immunization), as well as expression of therapeutic proteins, such as antibodies (e.g., for methods of treatment).