Zika virus disease vaccine taking human Ad5 replication-defective adenovirus as vector

Abstract

The invention discloses a codon-optimized nucleotide sequence capable of expressing an Env protein of a zika virus. The sequence can be fused with a protein prM and a protein prM endogenous signal peptide of a codon-optimized zika virus; after the sequence is inserted into a shuttle vector pDC316, the sequence and an auxiliary vector pBHGlox_E1, 3Cre realize cotransfection of a cell HEK293, so as to package an E1 and E3 combined missing-recombinant adenovirus taking a replication-defective human type-5 adenovirus as a vector; the recombinant adenovirus vector can efficiently express an envelope protein of the zika virus in an infected cell. After the nucleotide sequence-inserted recombinant adenovirus serving as a vaccine is immune to an animal for single time, strong humoral immune and cellular immune responses can be quickly induced. A zika vaccine taking the recombinant adenovirus as the vector is suitable for large-scale and rapid preparation and can be used for emergent vaccination for a large scale of people in a zika outbreak and prophylactic immunization for people at ordinary times.

Description

technical field [0001] The invention discloses a Zika virus disease vaccine using human Ad5 replication-defective adenovirus as a carrier, and belongs to the technical field of bioengineering. Background technique [0002] Zika virus (Zika Virus, ZIKV) is a single-stranded positive-sense RNA virus, and yellow fever virus (YellowFever), dengue virus (Dengue Fever), Japanese encephalitis virus (Japanese encephalitis virus, JEV), forest encephalitis virus (Tick-borne encephalitis virus, TBEV) and West Nile virus (WNV) belong to the Flavivirus genus of the Flavivirus family. ZIKV was first discovered in monkeys in the Zika Forest in Uganda in 1947. It is mainly transmitted by Aedes mosquitoes, and in a few cases, it can also be transmitted through mother-to-child transmission, sexual transmission and blood transfusion. ZIKV initially only had small-scale outbreaks and epidemics in a few areas: in 1952, seroepidemiological surveys in Uganda, Nigeria, and India showed that humans...

AI Technical Summary

Problems solved by technology

Each type has its own advantages and disadvantages: the advantage of inactivated ZIKV vaccine is that it is highly safe and suitable for specific groups such as pregnant women and children. There have been other approved inactivated flavivirus vaccines on the market before, but the disadvantage is that Multiple immunizations are required to generate sufficient protective immune responses, which is not conducive to the use of emergency immunization for large-scale populations; recombinant subunit vaccines also have the advantage of high safety, but their disadvantages also lie in the need for multiple immunizations. Approved recombinant subunit vaccines for flaviviruses

[0008] Based on the actual needs of Zika virus disease vaccination in the prior art field, and the ineffectiveness of existing vaccines in terms of preventive effect, as well as the technical difficulties in the application of the AdMax system, the applicant intends to conduct a Codon optimization, and rational design of the expression form of the antigen, so that its expression in eukaryotic cells is significantly increased, and it provides stronger immunogenicity and can induce higher levels of antibody recombination at the same dose Adenoviral Vector Zika Virus Disease Vaccine

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