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Vaccines for SARS-CoV-2 are increasingly available under emergency use authorizations; however, indications are currently limited to individuals twelve (12) years or older. They also involve intramuscular immunization, which does not directly stimulate local immunity in the respiratory tract, the primary site of SARS-CoV-2 infection, shedding and spread. While the major burden of COVID-19 disease is in adults, infection and disease also occur in infants and young children, contributing to viral transmission.

Human respiratory syncytial virus (RSV) continues to be the leading viral cause of severe acute lower respiratory tract disease in infants and children worldwide, and also is an important cause of morbidity and mortality in the elderly. A licensed vaccine or antiviral drug suitable for routine use remains unavailable. This invention relates to the use of murine pneumonia virus (MPV—previously known as pneumonia virus of mice, PVM—of family Pneumovirida e) as a vaccine vector expressing the RSV fusion protein F, the most important protective antigen of RSV.

Malaria continues to be a life-threatening disease, causing roughly 241 million cases and an estimated 627,000 deaths in 2020, mostly among African children, although in 2020 nearly half of the world’s population was at risk of malaria. There is a big financial burden for antimalarial treatment; direct costs (for example, illness, treatment, premature death) have been estimated to be at least US $12 billion per year and the cost in lost economic growth is many times more than that.

This invention relates to the derivation of two stable cell lines, SVG5F4 and SVG1OB1, which can be used to study JC-virus infection. SVG cells are a heterogeneous population of immortalized human fetal glial cells, which express SV40 large T antigen. They are capable of supporting JC virus infection; however, the culture is mixed and changes over time. The two SV40-derived cell lines described here are stable over many passages.

3D spheroids have emerged as powerful drug discovery tools given their high-throughput screening (HTS) compatibility. The present invention presents a method for generating functional neural spheroids with differentiated human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes at cell type compositions mimicking specific regions of the human brain.

Local inflammation processes are crucially important in the host defense against pathogens and for successful immunization because proinflammatory cytokines are necessary for initiation and propagation of an immune response. However, normal inflammatory responses are eventually terminated by physiological termination mechanisms, thereby limiting the strength and duration of immune responses, especially to weak antigens. The inventors have shown that adenosine A2a and A3a receptors play a critical role in down-regulation of inflammation in vivo.

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.