Construction method and application of avian influenza universal vaccine with spore probiotics as mucosal delivery vector

An avian influenza and vaccine technology, applied in the field of vaccines, can solve the problems of lack of sensitivity and specificity, low prediction accuracy, and inability to prevent the action of pathogens, so as to promote enhancement, ensure specificity and broad efficacy, and improve immune protection effect. Effect

Inactive Publication Date: 2016-09-21
SUN YAT SEN UNIV
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  • Claims
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Problems solved by technology

Although the above-mentioned prediction methods have achieved certain success, they obviously have some shortcomings: ① most of the methods develop prediction algorithms based on the primary sequence of the antigenic protein. - There are extensive and complex interactions between the peptide binding groove residues of class I molecules, these forces have not been fully considered in the existing prediction methods, which directly lead to low prediction accuracy, lack of sensitivity and specificity
Traditional influenza vaccination relies on injection, which cannot prevent the initial action of pathogens on the host mucosal surface, but can only solve the resulting post-infection problems. However, in the absence of infection, the main portal channel for influenza virus entry is Controlling the occurrence of infection in the nasopharyngeal mucosa will have a better preventive effect. So far, the vaccines that have been used in clinical practice have failed to meet these standards

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  • Construction method and application of avian influenza universal vaccine with spore probiotics as mucosal delivery vector
  • Construction method and application of avian influenza universal vaccine with spore probiotics as mucosal delivery vector
  • Construction method and application of avian influenza universal vaccine with spore probiotics as mucosal delivery vector

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Embodiment 1

[0054] The inventors of the present application used the Schistosoma japonicum 26kDa GST (Sj26GST) protein as a model antigen in the previous research, and used the Bacillus subtilis expression plasmid pUS186 to construct the Sj26GST gene in the downstream of the Bacillus subtilis capsid gene CotC promoter and its coding sequence, at WB600 The exogenous protein Sj26GST was highly expressed on the surface of spore capsid in the extracellular enzyme-deficient strain.

[0055] Using shuttle integration plasmids pDG1664 and pDG364, Sj26GST was integrated into the chromosome of Bacillus subtilis through double crossover replacement, and expressed on the outer surface of spore capsid by fusion with CotC or CotB; at the same time, Sj26GST was secreted and expressed in propagule cells by using the rrnO promoter of Bacillus subtilis. In addition, a multivalent antigen fusion expression system was constructed using endophytic spores of Bacillus subtilis, and tetanus toxin C fragment (TTF...

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Abstract

The invention provides host bacteria, and also provides an avian influenza universal vaccine; the avian influenza universal vaccine takes spore probiotics as a mucosal delivery vector. A CTL epitope peptide of H7N9 or other type A avian influenza virus subtypes, a cytokine IL-2 and a brevibacterium mucosal immune vaccine vector are organically combined for the first time and have complementary advantages. For the H7N9, H5N1, H5N6, H7N9, H7N2, H7N3, H7N7, H9N2, H10N7 and other type A avian influenza virus subtypes, a CTL epitope antigen is designed and screened, the spore vector is used for delivery of the antigen epitope; a spore and a spore-displayed recombinant IL-2 are used as adjuvants, and the immune type and immunoreaction level are regulated.

Description

technical field [0001] The invention relates to a vaccine, in particular to a construction method and application of a universal avian influenza vaccine using spore-type probiotics as a mucosal delivery carrier. Background technique [0002] The prerequisite for effective prevention and control of sudden outbreaks such as H7N9 is the rapid development of new universal vaccines. At present, most of the existing influenza vaccines adopt the traditional inactivation or cracking process. The screened virus strains are injected into fertilized eggs, and then a large number of multiplied viruses are extracted and injected into the human body after inactivation treatment. to produce antibodies against influenza. In this development process, the shortest time period from pathogen to production of vaccine is 6-8 months, and the output is limited. It is difficult for the produced vaccine to adapt to the rapid mutation of the antigen, and the effect of the vaccine is limited to a cer...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/75C12N1/21A61K39/145A61K39/39A61K48/00A61K38/20A61P31/16C12R1/125
CPCA61K38/2013A61K39/0003A61K39/08A61K39/12A61K39/39A61K48/005C12N1/20C12N15/75C07K14/005C07K14/32C07K14/33C07K14/43559C07K14/55A61K2039/523A61K2039/541A61K2039/53A61K2039/543A61K2039/542A61K2039/552A61K2039/55533A61K2039/57A61K2039/70C12N2760/16134Y02A50/30
Inventor 李丽陆家海
Owner SUN YAT SEN UNIV
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