HLA Specific human cytomegalovirus Multi-epitope adenovirus DNA Vaccine of Chinese population

A technology of human cytomegalovirus and nucleic acid vaccines, which is applied in the direction of antiviral agents, recombinant DNA technology, biochemical equipment and methods, etc., can solve the problem of difficult presentation of epitope vaccines, uneven population and ethnic spatial distribution, and inability to cause protection The problem of immune response and other problems, to overcome the effect of weak immunogenicity and strong immune effect

Inactive Publication Date: 2009-11-18
SHANDONG UNIV QILU HOSPITAL
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Problems solved by technology

Overseas research on HCMV epitope vaccines targets European and African populations, whose HLA genetic background is different from that of the Chinese population. The epitope vaccines developed by them are difficult to be presented by HLA molecules in the Chinese population, and cannot elicit an effective protective immune response
At present, there is no report on HCMV multi-epitope vaccine in China, and the spatial distribution of Chinese population and ethnicity is extremely uneven, and the spatial distribution of HLA gene frequency and haplotype frequency in the population is highly heterogeneous, so the development of HLA distribution for the Chinese population The HCMV tandem epitope vaccine with strong immune effect is the key to the prevention and control of HCMV in my country

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  • HLA Specific human cytomegalovirus Multi-epitope adenovirus DNA Vaccine of Chinese population
  • HLA Specific human cytomegalovirus Multi-epitope adenovirus DNA Vaccine of Chinese population
  • HLA Specific human cytomegalovirus Multi-epitope adenovirus DNA Vaccine of Chinese population

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Embodiment Construction

[0025] The present invention will be described in further detail below in conjunction with specific examples, but not as a limitation of the present invention.

[0026] Preparation of HLA-specific human cytomegalovirus multi-epitope adenovirus nucleic acid vaccine in Chinese population

[0027] 1. Epitope prediction and determination

[0028] Using the Chinese HLA I cumulative phenotype frequency spatial prediction system ("Journal of Immunology" 2005, Volume 21, No. 2, P136), select 14 HLA I gene loci for combination, such as figure 1 As shown, the HLA coverage rate of the Chinese population of the HCMV multi-epitope vaccine of the present invention is as high as 92.07% (75.49-99.99%). Then select 83 epitopes in 15 kinds of antigenic proteins (pp28, pp50, pp65, pp150, pp71, gH, gB, IE-1, IE-2, US2, US3, US6, US11, UL16, UL18) of HCMV, Among them, there are 76 CTL epitopes for the above-mentioned 14 HLA I gene loci (Table 1), and 7 Th epitopes for the HLAII gene loci (Table ...

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Abstract

The present invention discloses an HLA Specific human cytomegalovirus Multi-epitope adenovirus DNA Vaccine of Chinese population, which consists of human cytomegalovirus tandem sequence CTL*Th and adenovirus expression vector pAd5F35, wherein the human cytomegalovirus tandem sequence CTL*Th comprises a nucleotide sequence represented by SEQ ID No.1. The nucleotide sequence comprises the nucleotide sequences of 83 antigen epitopes of 15 encoding proteins of human cytomegalovirus. Furthermore, the sequence covers 14 HLA I allelomorphic gene sites and 7 HLA II allelomorphic gene sites. The coverage percent of the HCMV tandem epitope DNA vaccine representing excellent HLA is 92.07 percent in average, and is used for preventing the forming of HCMV disease in the steps of adhering, duplicating and re-activating of the virus. The in vetro experiment shows that the vaccine of the invention has excellent immune effect and overcomes the defects of inferior immunogenicity and limited immune range of the prior HCMV vaccine.

Description

technical field [0001] The invention relates to a nucleic acid vaccine and its construction and application, in particular to a human cytomegalovirus (HCMV) nucleic acid vaccine, that is, a Chinese population HLA-specific human cytomegalovirus multi-epitope adenovirus nucleic acid vaccine and its construction and application. Background technique [0002] HCMV disease has become a common and important complication of organ transplantation and intrauterine infection, and is an important cause of transplantation failure, fetal death and malformation. Existing HCMV vaccines have shortcomings such as weak immunogenicity, limited immune range, and small immune response, and cannot effectively prevent and treat HCMV infection, mainly because: (1) the part that can really cause immune response in the antigen molecule is the one that is compatible with the host The antigenic epitope specifically bound by the human leukocyte antigen (HLA) molecule is the most basic structural and fun...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K39/245A61P31/22C12N15/85C12R1/93
Inventor 马道新纪春岩赵平薛付忠
Owner SHANDONG UNIV QILU HOSPITAL
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