KR-20260067425-A - Highly effective severe fever with thrombocytopenia syndrome vaccine composition based on recombinant vesicular stomatitis virus

Abstract

The present invention relates to a high-efficiency severe fever with thrombocytopenia syndrome (SFTS) vaccine composition based on a recombinant vesicular stomatitis virus. The above vaccine composition is characterized by being able to effectively express severe fever with thrombocytopenia syndrome virus antigen proteins, effectively induce an immune response even in small amounts, and use of a single serotype vaccine composition for both priming and boosting immunization.

Inventors

• 김다비
• 이정화
• 추승호
• 송만기
• 최정아
• 서동원
• 채인경

Assignees

• (주)크레오에스지

Dates

Publication Date

20260513

Application Date

20241104

Claims (7)

1. 1) Recombinant vesicular stomatitis virus Indiana serotype GML mutation (rVSVInd-GML); 2) Bullous stomatitis virus linker (intergenic junction); and 3) A polynucleotide consisting of SEQ ID NO. 6 encoding the severe fever with thrombocytopenia syndrome virus glycoprotein;
2. Vaccine composition comprising the polynucleotide of claim 1
3. In paragraph 2, the vaccine composition is characterized by further comprising one or more selected from the group consisting of preservatives, diluents, adjuvants, and carriers.
4. In paragraph 2, the vaccine composition is characterized as being for the prevention of severe fever with thrombocytopenia syndrome virus infection disease.
5. In paragraph 2, the vaccine composition is characterized in that it can be used as one or more selected from the group consisting of a priming vaccine composition and a vaccine composition.
6. A method for inducing an immune response against severe fever with thrombocytopenia syndrome virus in mammals, comprising the step of administering the vaccine composition of claim 2.
7. A method for inducing an immune response against severe fever with thrombocytopenia syndrome virus, characterized in that, in claim 6, the administering step comprises: a step of inducing a priming immune response; and a step of inducing a boosting immune response.

Description

Highly effective severe fever with thrombocytopenia syndrome vaccine composition based on recombinant vesicular stomatitis virus The present invention relates to a high-efficiency severe fever with thrombocytopenia syndrome vaccine composition based on a recombinant vesicular stomatitis virus. Severe Fever with Thrombocytopenia Syndrome (SFTS) is a term referring to a disease characterized by high fever and thrombocytopenia as its primary symptoms, as the name suggests. It is caused by infection with the SFTS virus. The disease is transmitted by the tick *Haemaphysalis longicornis*, a member of the family *Ixodidae* within the order Ixodiptera that acts as a vector for the SFTS virus. It refers to a disease in which the virus carried by the tick enters the body during blood-feeding, multiplies, and causes clinical symptoms. Since SFTS is transmitted by ticks, it is known to infect various animal species, including livestock, wild animals, and birds, that may be exposed to ticks. Among wild animals inhabiting Korea, infection has been confirmed in water deer and wild boars. The pathogen causing SFTS is the membrane-bound SFTS virus, which is spherical in shape with a diameter of 80–100 nm and belongs to the family Phenuiviridae, the genus Phlebovirus, and the genus Huaiyangshan banyangvirus. The genome is a single-stranded RNA with either positive or negative sense, containing three segments (L, M, S). The L (large) segment is 6,368 bp in size and encodes RNA-dependent RNA polymerase (RdRp); the M (medium) segment is 3,378 bp and encodes two glycoproteins (Gn/Gc); and the S (small) segment is 1,746 bp and encodes a nucleocapsid and a nucleoprotein. SFTS is primarily transmitted through tick bites. While it is presumed to be spread by ticks belonging to the family Ixodidae (often without visible bite marks), contact transmission via the blood or bodily fluids of infected animals has also been reported. The hard ticks that act as vectors for SFTS inhabit the entire country, and ticks infected with the virus causing SFTS have been detected. Therefore, caution should be exercised during outdoor activities from spring to autumn, when small ticks are active. For livestock and agricultural workers who require special management, minimizing contact with ticks is the best preventive measure. The glycoprotein (GP) of the SFTS virus is the only protein exposed on the surface of the viral particle and plays an essential role in the process of host cell entry. The glycoprotein is produced when a glycoprotein precursor expressed from the mRNA of the M genome is cleaved by proteases into mature Gn and Gc proteins, which are then inserted into the viral surface as a multimer. Gn and Gc proteins are essential for viral cell entry and binding; they interact with specific host cell receptors (lectin dendritic-cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)) to enable the virus to attach to the cell surface, strengthen contact between the virus and the dendritic cell membrane, and facilitate the fusion of the two membranes. Because the SFTS virus glycoprotein acts upon host receptors to coordinate viral attachment and entry, and is also a crucial factor in inducing an immune response, it is considered a primary vaccine target. Since there is currently no vaccine available to prevent severe fever with thrombocytopenia syndrome, there is a need to develop a vaccine. Based on this necessity, this application relates to the development of a vaccine that induces an effective immune response against the SFTS virus, the first of its kind in Korea. Figure 1 schematically shows a structure expressing the severe fever with thrombocytopenia syndrome virus glycoprotein of the present invention. Figure 2 schematically shows the matrix gene (M gene) mutation of the Indiana serotype (VSVInd-GML), a non-pathogenic vesicular stomatitis virus (VSV). Figure 3 shows the vector maps of prVSV-SFTS-GP and prVSV-SFTS-Gn. Figure 4 shows the results of the restriction enzyme assay of the prVSV-HFRS-GP vector. Figure 5 shows the results of SDS-PAGE analysis after purification of the severe fever with thrombocytopenia syndrome virus vaccine composition of the present invention. Figure 6 shows the results of a Western blotting analysis of the severe fever with thrombocytopenia syndrome virus vaccine composition of the present invention. Figure 7 shows the schedule and analysis results of the immune effect test of the severe fever with thrombocytopenia syndrome virus vaccine composition of the present invention. Figure 8 shows the results of the immunogenicity evaluation (ELISpot) of the severe fever with thrombocytopenia syndrome virus vaccine composition of the present invention. Figure 9 shows the schedule for the challenge protection test of the severe fever with thrombocytopenia syndrome virus vaccine composition of the present invention. Figure 10 shows the results of a challenge protection test of the severe fever with