Adenoviral vector-based vaccine against enterovirus infection
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An enterovirus and recombinant adenovirus technology, applied in the field of immunity, can solve the problems of inducing immunogenicity and obstruction
Active Publication Date: 2017-05-31
NAT INST OF HEALTH REPRESENTED BY THE SEC OF THE DEPT OF HEALTH & HUMAN SERVICES NAT INST OF HEALTH
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However, proteins of VLPs produced by non-human cells with different subsequent modifications (such as glycation) may induce different immunogenicity in humans
In addition, there are obstacles in the production of highly purified VLPs
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[0082] In this study, we have designed and genetically engineered a recombinant adenoviral vector, Ad-EVVLP, carrying EV71P1 and 3CD genes, which were inserted into the E1 / E3 deleted adenoviral genome. Ad-EVVLP can be produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLP) are formed by physically linking with EV71-type capsid proteins VPO, VP1 and VP3; wherein these capsid proteins are the products of the P1 gene. The virus particles were cleaved by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, and identified by transmission electron microscopy and western blotting. Immunogenicity studies in mice showed that Ad-EVVLP-immunized antisera can neutralize EV71 type B4 and C2 genotypes. VLP-specific CD4 + and CD8 + Activation of / IFN-γ T cells is associated with the induction of Th1 / Th2-balanced IFN-, IL-17, IL-4, and IL-13; in contrast, FI-EV71 only induces Th2-mediated neutralization Antibody against EV71 and low VLP-...
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Abstract
The present invention relates to a recombinant adenoviral vector for generating immunity against enterovirus infection. In one embodiment, the recombinant adenoviral vector of the invention comprises an expression cassette encoding a PI protein and a 3 CD protease of an enterovirus. In another embodiment, the recombinant adenoviral vector of the invention comprises an expression cassette encoding a 3C protease or a 3CD protease of an enterovirus. The present invention also relates to a vaccine composition comprising the recombinant adenoviral vector as described. A method of inducing an immune response in a subject against enterovirus infection using the recombinant adenoviral vector and the vaccine composition is provided. Further provided is a method for producing virus like particles of an enterovirus by expressing the adenoviral vector as described herein in mammalian cells.
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[0001] Related applications [0002] This case is based on 35 U.S.C. §119(e), claiming priority based on U.S. Provisional Patent Application No. 61 / 985,803 filed on April 29, 2014, the entire contents of which are incorporated herein by reference. technical field [0003] The present invention relates generally to the field of immunization and, in particular, to adenoviral vector-based vaccines against enteroviral infections. Background technique [0004] Enteroviruses, belonging to the Picornaviridae family, are tiny, non-enveloped viruses containing positive strand RNA. The Enterovirus genus now includes 12 species: Enterovirus A, Enterovirus B, Enterovirus C, Enterovirus D, Enterovirus E, Enterovirus F, Enterovirus G, Enterovirus H, Enterovirus J, Rhinovirus A, Rhinovirus Virus B and rhinovirus C. These viruses infect the intestinal tract, but can cause various types of diseases. Typical enteroviral diseases are meningitis, paralysis, myocarditis, hand, foot and mouth ...
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