KR-20260067424-A - Highly effective Hemorrhagic fever with renal syndrome vaccine composition based on recombinant vesicular stomatitis virus

Abstract

The present invention relates to a high-efficiency hemorrhagic fever with renal syndrome vaccine composition based on a recombinant vesicular stomatitis virus. The above vaccine composition is characterized by being able to effectively express a hantavirus antigen protein, effectively induce an immune response even with a small amount, and use of a single serotype vaccine composition for both priming and boosting immunization.

Inventors

• 이정화
• 김다비
• 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 a hantavirus 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 Hantavirus 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 to Hantavirus in mammals comprising the step of administering the vaccine composition of claim 2
7. A method for inducing an immune response against Hantavirus according to claim 6, wherein the administering step comprises: a step of inducing a priming immune response; and a step of inducing a boosting immune response.

Description

Highly effective hemorrhagic fever with renal syndrome vaccine composition based on recombinant vesicular stomatitis virus The present invention relates to a high-efficiency hemorrhagic fever with renal syndrome vaccine composition based on a recombinant vesicular stomatitis virus. Hemorrhagic fever with renal syndrome (HFRS) is an infection caused by Hantavirus, characterized by fever, high fever, renal failure, and hemorrhage, and is classified as a Class 3 statutory infectious disease in Korea. Hantavirus particles are spherical particles with a diameter of approximately 100 nm that possess an envelope, and the envelope contains the glycoproteins G1 and G2 proteins. The genome of Hantavirus is a negative-sense single-stranded RNA and has three segmented genomes. The three genomes are classified into L (Large), M (Middle), and S (Small) RNA genomes according to size, and the combined size of the three segments reaches approximately 12 to 19 kilobases (kb). In each segment of the genome, one type of mRNA is transcribed, RNA-dependent RNA polymerase (RdRp) is expressed in the L genome, two glycoproteins (G1, G2) are expressed in the M genome, and a nucleocapsid is expressed in the S genome. Hemorrhagic Fever with Renal Syndrome (HFRS), also known as epidemic hemorrhagic fever, is primarily caused in Korea by viruses such as the Hantaan virus and the Seoul virus. It is a viral infectious disease characterized by systemic hemorrhage, with the main symptoms appearing as fever, chills, headache, back pain, and muscle pain following an asymptomatic incubation period of 2 to 3 weeks. HFRS became known during the Korean War through research on fever patients exhibiting hemorrhagic tendencies, and the causative virus was first isolated and identified from the lung tissue of striped field mice in 1976. Rodents are known to act as vectors for Hantavirus; viruses secreted through the excrement, such as urine, saliva, and feces, of infected rodents like striped field mice and house mice dry out and float in the air, eventually infecting humans through the respiratory system or direct contact. Infections caused by Hantavirus induce different clinical syndromes depending on the strain; it is reported that it primarily causes Hemorrhagic Fever with Renal Syndrome (HFRS) in Europe and Asia, and Hantavirus Cardiopulmonary Syndrome (HCPS) in North and South America. In Europe and Asia, Hantavirus, Suelle virus, and Pumalla virus are known to be the main causes of infection, while in North and South America, infections caused by Sin Nombre virus and Andean virus are primarily reported. Globally, the number of patients infected with Hantavirus is reported to exceed approximately 200,000 annually. Reports indicate that the mortality rate for HFRS reaches 5–15%, while for HCPS it can reach as high as 40%. Since the virus is transmitted by rodents, the incidence rate is high among farmers in forested areas with large rat populations or during the harvest season, and the risk of infection is high during outdoor activities. Therefore, as the population engaging in outdoor activities such as hiking and camping increases, it is urgent to expand prevention to the general public, and the need for preventive vaccines capable of effectively blocking infection by various hantaviruses is emerging worldwide. Hantavirus glycoproteins (GPs) are the only proteins exposed on the surface of viral particles and play an essential role in the process of host cell penetration. Glycoproteins are produced when glycoprotein precursors expressed in the mRNA of the M genome are cleaved by proteases into mature G1 and G2 proteins. G1 and G2 proteins are essential for viral cell penetration and binding; they interact with specific receptors on host cells (beta-3-integrin) to enable the virus to attach to the cell surface, strengthen contact between the virus and the cell membrane, and facilitate the fusion of the two membranes. Because Hantavirus glycoproteins act upon host receptors to coordinate viral attachment and entry, and are also important factors in inducing an immune response, they are considered a primary vaccine target. Currently, Hantavax, a recombinant protein vaccine containing glycoproteins G1 and G2, is administered to 150,000 people annually; however, it is reported that only 10.7% of vaccinated individuals possess antibodies 11 months after the third dose. Although domestically produced vaccines exist, they exhibit low long-term immunogenicity and seroconversion rates, necessitating up to four additional doses. Therefore, there is a need for a new improved vaccine that reduces the number of vaccinations while enhancing efficacy. Based on this need, the present application relates to the development of a vaccine that induces an effective immune response against the virus causing hemorrhagic fever with renal syndrome (HFRS). Figure 1 schematically shows a structure expressing the hantavirus glycoprotein of the present invention. Figure 2 s