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.

Orthotospovirus virions travel through the thrips foregut and enter midgut epithelial cells through the interaction between virus glycoproteins and cellular receptors with several protein motifs thought to be involved in the interaction. Single, double and triple mutant polypeptides in the soybean vein necrosis virus (SVNV)/Neohydatothrips variabilis system are provided herein and several are shown to block viral transmission from the thrips to the soybean plants. Methods for inhibiting viral transmission using these polypeptides or constructs comprising polynucleotides encoding peptides are also provided herein.

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.

The invention relates to methods of diagnosis or detection of Moissiacense virus, a novel orthobunyavirus causing human encephalitis, comprising determining the presence of at least one nucleic acid or protein of said virus or antibodies thereto, in a biological sample. The invention also relates to the various diagnostic agents derived from the viral nucleic acids or proteins, in articular nucleic acid primers and probes, antigens and antibodies, and their use for the diagnosis of Moissiacense virus infection and associated disease, in particular encephalitis. The invention further relates to antigens derived from the viral proteins as vaccine for the prevention of Moissiacense virus infection and associated disease, in particular encephalitis.

Orthotospovirus virions travel through the thrips foregut and enter midgut epithelial cells through the interaction between virus glycoproteins and cellular receptors with several protein motifs thought to be involved in the interaction. Single, double and triple mutant polypeptides in the soybean vein necrosis virus (SVNV)/Neohydatothrips variabilis system are provided herein and several are shown to block viral transmission from the thrips to the soybean plants. Methods for inhibiting viral transmission using these polypeptides or constructs comprising polynucleotides encoding peptides are also provided herein.

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.

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.

The present disclosure relates to DNA vaccines against Crimean-Congo Hemorrhagic Fever (CCHF) virus. The present disclosure also relates to CCHF virus sequences and their use for vaccination such as DNA vaccination. The present disclosure more particularly relates to artificial nucleic acid molecules that are able to encode a CCHF polypeptide of an infectious CCHF virus, a fragment or a variant thereof. The nucleic acid molecules of the present application are formulated as immunogenic compositions.

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.