RSV is the most important viral agent of severe respiratory disease in infants and young children worldwide and also causes substantial morbidity and mortality in older adults. RSV is estimated to cause more than 33 million lower respiratory tract illnesses, three million hospitalizations, and nearly 200,000 childhood deaths worldwide annually, with many deaths occurring in developing countries. However, despite the prevalence of RSV and the dangers associated with infection, no RSV vaccine has been successfully developed to date.

SARS-CoV-2 has resulted in a global pandemic, sparking urgent vaccine development efforts. The trimeric SARS-CoV-2 spike stabilized in its prefusion conformation by the addition of 2 proline mutations (“SARS-CoV-2 S2P”) is the antigenic basis of SARS-CoV-2 vaccines that are currently authorized for use in the United States.

Atopic dermatitis (AD) is a common, recurrent, chronic inflammatory skin disease that is a cause of considerable economic and social burden. It is one of the most prevalent skin disorders, affecting ~25% of children in developed and developing countries and is expected to continue to escalate. This increased rate of incidence has changed the focus of research on AD toward epidemiology, prevention, and treatment.

Worldwide, 130-150 million individuals are chronically infected with hepatitis C virus (HCV), a major cause of liver-associated morbidity and mortality worldwide. Despite recent advances in antiviral drugs that can cure some individuals, a rapid decline of the global disease burden is hampered by remarkably high treatment costs and a high number of undiagnosed infections. Moreover, a significant number of patients develop resistance and additional treatment modalities may be needed to dramatically reduce the worldwide incidence of HCV infection.

The invention provides immunogen polypeptides comprising fragments of VAR2CSA protein expressed by P. falciparum as potential second-generation placental malaria vaccine candidates. VAR2CSA is the leading antigen target for a placental malaria vaccine, where associated antibody titers are correlated with protection. Aspects of the inventive immunogen polypeptides comprise all or portions of the chondroitin sulfate A (CSA) binding regions of VAR2CSA, as identified by a structural study of VAR2CSA conducted by the inventors, that possess great sequence conservation among P.

The current invention provides nucleic acid sequences comprising the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and 1b. 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.

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.

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 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.

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.