Multivalent live influenza vaccine platform using recombinant adenovirus
Inventors
YOUN, Hyun Joo • HAN, EUN YEONG
Assignees
Geneuin-Tech Co Ltd • Industry Academic Cooperation Foundation of Inje University
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Publication Number
US-11672854-B2
Publication Date
2023-06-13
Expiration Date
Abstract
The present invention relates to a multivalent live influenza vaccine platform using a recombinant adenovirus. The present invention is a live attenuated vaccine platform using a recombinant virus and it is easy to inoculate because it is infected with the respiratory tract like influenza virus and exhibits a vaccine action and it is a multivalent vaccine which combines two types into one and it is a highly novel vaccine that does not need to mix viruses compared to vaccines using multiple combinations of one vaccine. The present invention is the first vaccine in which a gene obtained by fusion of two influenza antigen genes into one gene is incorporated into a recombinant virus. Instead of using the entire HA gene of influenza, but using a structurally independent HA1 gene, which is about half of the total HA gene, several types of HA genes could be fused into one. When the recombinant virus was inoculated into mice by nasal inhalation, it was confirmed that it is an effective vaccine in which the vaccine effect is induced by two inoculations, and the vaccine platform of the present invention is expected to be useful for the development of a vaccine for human influenza infection.
Core Innovation
The invention relates to a multivalent live attenuated influenza vaccine platform using a recombinant adenovirus that expresses a fused influenza HA1 antigen. The platform is based on a recombinant adenovirus carrying a single gene construct encoding a fused H5 HA1 linked to H7 HA1, described as an H5/H7 HA1 fusion gene and a recombinant fusion protein (SEQ ID NO: 1). This fusion design combines two HA1 antigens into one recombinant viral particle rather than requiring separate virus mixing.
The problem addressed is the development of a multivalent live attenuated influenza vaccine. The disclosure emphasizes the use of HA1 antigens and the goal of expressing the fused antigen to induce an immune response. The document frames delivery as targeting the respiratory tract, with intranasal instillation/inhalation being highlighted for easy inoculation.
The document further describes experimental confirmation of the construct and immune response. It reports fusion protein expression in the recombinant adenovirus and induction of antibodies against the fusion protein in immunized mice, with antibody measurement described using ELISA and comparison using a GFP control adenovirus. The disclosure supports that administering the recombinant adenovirus vaccine can induce an anti-fusion-protein antibody response after two intranasal inoculations in BALB/c mice.
Claims Coverage
The independent claims identified are claim 1 and claim 5. Across these claims, the core inventive features focus on the H5 HA1/H7 HA1 fused antigen and its production via a recombinant adenovirus, with defined expression-vector composition elements and sequence identifiers.
H5 HA1/H7 HA1 recombinant fusion protein produced by recombinant adenovirus
A recombinant fusion protein of influenza A virus H5 type hemagglutinin 1 (HA1) and H7 type HAL obtained from a recombinant adenovirus strain transfected with a recombinant expression vector comprising an influenza A virus H5 type hemagglutinin 1 (HA1) gene and an influenza A virus H7 type HA1 gene.
Expression-vector arrangement with ribosome binding site, linker, and tag gene
A recombinant expression vector for producing the recombinant fusion protein comprising, in order, a ribosome binding site, an influenza A H5 HA1 gene, a linker, an influenza A H7 HA1 gene, and a tag gene.
Defined H5 and H7 HA1 gene sequence identities via SEQ ID numbers
A recombinant fusion protein wherein the influenza A virus H5 HA1 gene is represented by SEQ ID NO: 2 and the influenza A virus H7 HA1 gene is represented by SEQ ID NO: 3.
Defined fusion protein sequence via SEQ ID NO: 1
A recombinant fusion protein defined by SEQ ID NO: 1.
Preparing recombinant adenovirus particles by transfecting with H5 HA1/H7 HA1 expression vector and culturing
A method of preparing recombinant adenovirus particles comprising transfecting adenovirus with a recombinant expression vector comprising an influenza virus H5 type HA1 gene and an influenza virus H7 type HA1 gene, and culturing transfected adenovirus.
Recombinant adenovirus particles expressing H5 HA1/H7 HA1 fusion proteins
The method prepares recombinant adenovirus particles that express influenza virus H5 HA1 and H7 HA1 recombinant fusion proteins.
Fusion protein corresponds to SEQ ID NO: 1 in recombinant adenovirus particles
The recombinant fusion protein expressed by the recombinant adenovirus particles corresponds to SEQ ID NO: 1.
Overall claim coverage centers on a recombinant H5 HA1/H7 HA1 fusion protein defined by SEQ ID NO: 1 and supported by defined gene representations (SEQ ID NO: 2 and SEQ ID NO: 3), and on recombinant adenovirus particle preparation by transfecting adenovirus with an expression vector carrying the H5 and H7 HA1 genes followed by culturing.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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