The present invention is directed to an artificial nucleic acid, particularly to an artificial RNA, and to polypeptides suitable for use in treatment or prophylaxis of an infection with a virus of the order Bunyavirales, particularly Severe fever with thrombocytopenia syndrome virus (SFTSV), Rift Valley fever virus (RVFV), or Crimean-Congo hemorrhagic fever virus (CCHFV), or a disorder related to such an infection. The present invention further concerns a Bunyavirales vaccine, particularly a SFTSV, RVFV, or CCHFV vaccine. The present invention is directed to an artificial nucleic acid, polypeptides, compositions and vaccines comprising the artificial nucleic acid or the polypeptides. The invention further concerns a method of treating or preventing a disorder or a disease, first and second medical uses of the artificial nucleic acid, polypeptides, compositions and vaccines. Further, the invention is directed to a kit, particularly to a kit of parts, comprising the artificial nucleic acid, polypeptides, compositions and vaccines.

Certain embodiments are directed to an improved RVF vaccine for human use, and method for producing the same.

The present invention relates to the field of (vector) vaccines, and especially to novel promoter sequences, expression cassettes and vectors, which are suitable to express genes of interest, especially antigen encoding sequences. The viral vectors of the present invention are useful for producing an immunogenic composition or vaccine.

The genetically modified nairoviruses of this invention possesses a viral ovarian tumor protease with decreased ability to remove ubiquitin (Ub) and ISG15 tags that the human organism uses to label proteins for removal. Exemplary are Crimean-Congo hemorrhagic fever virus and Erve virus. Unlike complete knockout strains, the modified virus retains enough activity for replication in a human cell line. This creates an immunogenic and non-pathogenic virus that can be used as an effective live vaccine agent for prophylaxis and treatment.

The present invention relates to a novel genotype of severe fever with thrombocytopenia syndrome viruses and use thereof as an immunogenic composition. The severe fever with thrombocytopenia syndrome viruses of the present invention are genetically different from conventional severe fever with thrombocytopenia syndrome viruses and are novel viruses taxonomically belonging to three sub-groups of genotype B. In view of the vaccine property that specific genotype viruses alone show only limited protective potential, the novel viruses of the present invention may be advantageously used as a vaccine having excellent cross-immunogenicity for SFTSV.

Crimean-Congo hemorrhagic fever (CCHF) virus replicon particles (VRP) are described. These VRP are capable of undergoing a single round of virus replication, but are unable to produce new particles or spread to neighboring cells due to the lack of the glycoprotein-encoding M genome segment. In some instances, the VRP contain one or more mutations in the viral ovarian tumor domain protease encoded by the L genome segment or heterologous antigens within its S genome segment. The VRP are shown to elicit a protective immune response against lethal CCHF virus challenge in an animal model.

Certain embodiments are directed generally to compositions and methods related to recombinant vesicular stomatitis virus vectors (ΔGrVSV) encoding Crimean-Congo Hemorrhagic Fever glycoprotein precursor (CCHFV-GPC) and forming a recombinant vesicular stomatitis virus vector encoding Crimean-Congo Hemorrhagic Fever glycoprotein precursor (ΔGrVSV-CCHFV-GPC).

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. Limited evidence suggests that antibodies can protect humans against lethal CCHFV disease, but the protective efficacy of antibodies has never been evaluated in adult animal models. Here adult mice were used to investigate the protection provided by glycoprotein-targeting neutralizing and non-neutralizing monoclonal antibodies (mAbs) against CCHFV infection. A single non-neutralizing antibody (mAb-13G8) was identified that protected adult type I interferon deficient mice >90% when treatment was initiated prior to virus exposure and >60% when administered after virus exposure. Neutralizing antibodies known to protect neonatal mice from lethal CCHFV infection, failed to confer protection regardless of IgG subclass. The target of mAb-13G8 was identified as GP38, one of multiple proteolytically-cleaved glycoproteins derived from the CCHFV glycoprotein precursor polyprotein. Robust protection required complement activity, but not Fc-receptor functionality. Consistently, it was found that GP38 previously identified as a secreted molecule also localizes to viral envelope and cellular plasma membranes. This study reveals GP38 as an important antibody target for CCHFV and lays the foundation to develop novel vaccines and immunotherapeutic against CCHFV in human.

Arbovirus carries an altered furin cleavage site that results in enhanced cleavage of a precursor polyprotein, such as, prE2 or prM. Dengue virus particles can have an amino acid alteration within amino acids 80-130 of prM. Zika virus particles can have alterations at amino residues at and/or about the furin cleavage site. The virus can be produced in insect cells. The virus does not form progeny virus in mammal cells.

The present disclosure provides vectors that allow efficient expression of transgenes. The vector of the present disclosure may be used to express proteins or peptides of interest into a host's cells and to trigger an immune response towards an antigenic portion of the proteins or peptides in a mammal. The vectors may be used for experimental research, for pre-clinical or clinical application. The vectors disclosed herein induce both cell-mediated and humoral immune responses and may be used in DNA vaccination.