Orthobunyavirus in human encephalitis and its diagnostic and therapeutic applications
Inventors
Eloit, Marc • Perot, Philippe • SEILHEAN, Danielle • DUYCKAERTS, Charles • CHRETIEN, Delphine
Assignees
Centre National de la Recherche Scientifique CNRS • Assistance Publique Hopitaux de Paris APHP • Institut National de la Sante et de la Recherche Medicale INSERM • Ecole Nationale Veterinaire de Maisons-Alfort ENVA • Sorbonne Universite • Institut du Cerveau et de La Moelle Epiniere ICM • Institut Pasteur
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Publication Number
US-12529114-B2
Publication Date
2026-01-20
Expiration Date
Abstract
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.
Core Innovation
The invention concerns the discovery that Moissiacense virus, an orthobunyavirus within the Umbre/Koongol-related clade, is a cause of human encephalitis and enables Moissiacense virus diagnosis and detection. It also provides implications for prevention through vaccine or immunogenic compositions using selected viral antigens. The described diagnostic approach targets viral nucleic acids or viral proteins and corresponding antibodies in clinical and arthropod-vector samples.
A central part of the invention defines Moissiacense virus genome segment targets, linking the S, M, and L segments to the encoded nucleocapsid (N), polyprotein M (cleaved to Gn/NSm/Gc), and polymerase (L) core polymerase domain functions. The nucleic-acid detection is grounded in specific S, M, and L sequence regions associated with species-specific Moissiacense detection, including identity thresholds and complement targets. Genomic segments are described with functions such that S corresponds to N and NSs, M corresponds to Gn/NSm/Gc, and L corresponds to RNA-dependent RNA polymerase activity.
The invention further describes antigen and antibody detection concepts using immunoassays with N, Gn, and Gc proteins and antibody-binding extracellular fragments or epitopes. Diagnostic kit concepts are provided in which probes/primers are combined with amplification and/or detection reagents, and differential diagnosis can be performed by multiplexing other encephalitis pathogens. Supporting context is provided through metatranscriptomics from brain tissue of encephalitis cases identifying Umbre/Koongol-related sequences and yielding full S/M/L coding sequences, and through detection of Koongol-like sequences in a mosquito capture with Moissiacense negatives, together with serological screening using Gc head ELISA/LIPS.
Claims Coverage
The document provides three independent claim groups covering detection of Moissiacense virus nucleic acid (S, M, L segments), detection of Moissiacense virus antigen or antibody, and diagnostic/preventive compositions via kits and an immunogenic/vaccine pharmaceutical composition. Across these independent claims, the inventive features focus on defined sequence identity/region constraints for S/M/L nucleic acids, defined antibody-binding antigen sequences or fragments, and kit composition including probes/primers and amplification/detection reagents, optionally with immunogenic active substances plus pharmaceutically acceptable adjuvant.
Moissiacense nucleic-acid detection by S/M/L segment identity targets
A method of detection of Moissiacense virus nucleic acid in a sample by determining the presence of at least one viral nucleic acid selected from S, M, and L segment nucleic acids, where the S segment comprises a sequence having at least 80% identity with SEQ ID NO: 1 (or complement) encoding N with at least 90% identity with SEQ ID NO: 2, the M segment comprises a sequence having at least 80% identity with SEQ ID NO: 3 (or complement) encoding polyprotein M with at least 90% identity with SEQ ID NO: 4, and the L segment comprises a sequence having at least 80% identity with SEQ ID NO: 5 (or complement) encoding polymerase (L) with at least 90% identity with SEQ ID NO: 6 including at least 90% identity in the core polymerase domain.
Moissiacense antigen or antibody detection by antigen-antibody complex detection
A method of detection of Moissiacense virus antigen or antibody in a sample comprising incubating an antigen from Moissiacense virus or antibody thereto with the sample to form a mixture and detecting antigen-antibody complexes in the mixture.
Moissiacense nucleic-acid detection kit with Moissiacense-specific probe/primer sets
A kit for the detection of Moissiacense virus nucleic acid comprising at least one oligonucleotide probe or primer selected from 5 to 100 nucleotides, preferably 15 to 60 nucleotides, having 80% to 100% identity with any of SEQ ID NO: 1, 3, 5, and 7 to 9 specific for Moissiacense virus, and their complement, and reagents for amplification of a target sequence and/or detection of an amplification product.
Moissiacense antigen/antibody detection kit with defined antibody-bound antigen sequences and amplification/detection reagents
A kit for the detection of Moissiacense virus antigen or antibody comprising an antigen from Moissiacense virus or an antibody thereto, where the antigen comprises an amino acid sequence selected from sequences having 90 to 100% with SEQ ID NO: 2 or a fragment of at least 10 amino acids bound by antibodies against Moissiacense virus; sequences having 90 to 100% identity with SEQ ID NO: 58 or 60 or a fragment of at least 10 amino acids bound by antibodies against Moissiacense virus; an extracellular fragment of SEQ ID NO: 58 of at least 10 amino acids bound by antibodies against Moissiacense virus; and a fragment consisting of the sequence of any of SEQ ID NO: 61 to 64 bound by antibodies against Moissiacense virus, together with reagents for amplification of a target sequence and/or detection of an amplification product.
Immunogenic/vaccine composition with defined Moissiacense antigens plus pharmaceutically acceptable adjuvant
An immunogenic or vaccine pharmaceutical composition comprising as active substance an antigen from Moissiacense virus with an amino acid sequence selected from sequences having 90 to 100% with SEQ ID NO: 2 or a fragment of at least 10 amino acids bound by antibodies against Moissiacense virus; sequences having 90 to 100% identity with SEQ ID NO: 58 or 60 or a fragment of at least 10 amino acids bound by antibodies against Moissiacense virus; an extracellular fragment of SEQ ID NO: 58 of at least 10 amino acids bound by antibodies against Moissiacense virus; and a fragment consisting of the sequence of any of SEQ ID NO: 61 to 64 bound by antibodies against Moissiacense virus, wherein the composition further comprises at least one pharmaceutically acceptable adjuvant.
Overall, claim coverage centers on Moissiacense virus detection and prevention using explicitly defined S/M/L nucleic-acid targets with identity thresholds, antigen/antibody detection through antigen-antibody complex formation, and composition of diagnostic kits containing Moissiacense-specific probes/primers and amplification/detection reagents. In parallel, an immunogenic/vaccine composition is defined using specific antibody-bound antigen sequences or fragments together with a pharmaceutically acceptable adjuvant.
Stated Advantages
Enables diagnosis/detection of Moissiacense virus associated with human encephalitis.
Supports differential diagnosis of human encephalitis by multiplexing other encephalitis pathogens.
Enables detection using Moissiacense virus nucleic acids and/or Moissiacense virus proteins and corresponding antibodies.
Provides preventive composition concepts using selected viral antigens and adjuvants.
Documented Applications
Diagnosis of encephalitis in humans for differential diagnosis of human encephalitis.
Detection of Moissiacense virus nucleic acid in clinical samples such as brain biopsy, cerebral spinal fluid, whole blood, plasma, or serum.
Epidemiological survey by detecting Moissiacense virus nucleic acid in an arthropod vector population.
Diagnostic kit use for detecting Moissiacense virus nucleic acid.
Diagnostic kit use for detecting Moissiacense virus antigen or antibody.
Vaccine/prevention using an immunogenic or vaccine pharmaceutical composition comprising Moissiacense virus antigens and a pharmaceutically acceptable adjuvant.
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