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Preparation and application of influenza virus-carried HAdV (human adenovirus) chimeric vaccine

A technology of influenza virus and chimeric vaccine, applied in the direction of virus/phage, virus, antiviral agent, etc., can solve the problems of inconvenience, non-ideal immune route, low neutralizing antibody titer, etc.

Active Publication Date: 2014-06-18
THE FIFTH MEDICAL CENT OF CHINESE PLA GENERAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As early as the 1960s, the United States had used enteric-coated live attenuated adenovirus vaccines to conduct immunization experiments on adults in boot camps, and found that it could reduce the fever symptoms caused by adenoviruses by 90%. Clinical testing found that the neutralizing antibody titer induced by this live vaccine was very low
In the 1970s, adenovirus enteric-coated live vaccine was used for immunization, and serum IgM, IgG, and IgA were found to be elevated, but no corresponding IgA antibodies were found in nasal secretions
For HAdV vaccines for respiratory mucosal infection, injection vaccination is not ideal and inconvenient

Method used

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  • Preparation and application of influenza virus-carried HAdV (human adenovirus) chimeric vaccine
  • Preparation and application of influenza virus-carried HAdV (human adenovirus) chimeric vaccine
  • Preparation and application of influenza virus-carried HAdV (human adenovirus) chimeric vaccine

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0082] Experimental example 1, the preparation of the HAdV chimeric vaccine rFLU-HAdV / NS1 of the chimeric HAdV-Hexon-L1 / L2 dominant antigen epitope of the influenza virus as the carrier

[0083] 1. The dominant epitope sequence of Hexon-L1 / L2 (HAdV-Hexon-L1 / L2) in HAdV type 3 and type 7 is shown in SEQ ID No.1, which has been verified by animal experiments and clinical patient serum, and meets the next step Experimental requirements.

[0084] 2. Construction of recombinant plasmid pHexon-L1 / L2-NS1

[0085] Using the NS1 gene fragment of the cold-adapted and attenuated influenza virus strain A / AA / 6 / 60 as the target for inserting the dominant epitope gene of HAdV-Hexon-L1 / L2, the recombinant plasmid pHexon-L1 / L2-NS1, the specific policy is as follows figure 1 As shown in A.

[0086] Specifically, the HAdV-Hexon-L1 / L2 dominant antigenic epitope gene is inserted into the coding gene of the first 125 amino acids of the NS1 gene open reading frame (ORF) of the cold-adapted and a...

Embodiment 3

[0137] Embodiment 3, the preparation of the HAdV chimeric vaccine rFLU-HAdV / NA of the chimeric HAdV-Hexon-L1 / L2 dominant epitope of the influenza virus as the carrier

[0138] 1. The dominant epitope sequence of HAdV-Hexon-L1 / L2 in HAdV types 3 and 7 is shown in SEQ ID No.1, verified according to the method of step 1 of Example 1, and meets the requirements of the next experiment.

[0139] 2. Construction of recombinant plasmid pHexon-L1 / L2-NA

[0140] Using the NA gene fragment of A / California / 07 / 2009 (H1N1) as the target for inserting the dominant epitope gene of HAdV-Hexon-L1 / L2, the recombinant plasmid pHexon-L1 / L2-NA was constructed by molecular biology methods, specifically Strategies such as figure 1 C shown.

[0141] Specifically, the HAdV-Hexon-L1 / L2 dominant antigen epitope gene was inserted into the first 183 nucleotides and the last nucleotide of the NA gene open reading frame (ORF) of the influenza virus strain H1N1 subtype A / California / 07 / 2009 that year. Betwe...

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Abstract

The invention discloses a preparation and application of an influenza virus-carried HAdV chimeric vaccine and a DNA (deoxyribonucleic acid) molecule represented by SEQ ID No.1. According to the HAdV chimeric vaccine disclosed by the invention, HAdV infectious disease pathogens can be covered, more crowds can be protected from being harmed by influenza viruses and HAdV, and foundations are laid for producing a 'dual-purpose vaccine' or a 'multi-purpose vaccine'.

Description

technical field [0001] The invention relates to the preparation and application of an HAdV chimeric vaccine with influenza virus as a carrier. Background technique [0002] Respiratory tract infectious diseases are still one of the main causes of death in the world, and adenovirus (Adenovirus, AdV) and influenza virus are important respiratory pathogens. As we all know, adenovirus is widely distributed in nature and is one of the common pathogens of children's respiratory diseases. About 5%-10% of acute upper respiratory tract infections in children under 3 years old are caused by adenovirus. From the clinical survey results of hospitalized children in northern and southern my country, it is confirmed that adenovirus types 3 and 7 are the main pathogens of adenovirus pneumonia, and the lower respiratory tract infections caused by them account for 50% of all adenovirus infections. Adenoviruses, due to their multiple types and wide range of pathogenicity, pose a serious thre...

Claims

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Application Information

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IPC IPC(8): C12N15/11C12N7/01A61K39/145A61K39/235A61P31/16A61P31/20
CPCA61K39/12A61K2039/5254A61K2039/5256A61P31/16A61P31/20C12N2710/10034
Inventor 杨鹏辉王希良张绍庚刘娜段跃强张培瑞李志伟王兆海
Owner THE FIFTH MEDICAL CENT OF CHINESE PLA GENERAL HOSPITAL
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