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

A technology for Zika virus and replication defects, applied in the field of bioengineering, can solve the problems of inefficient vaccine prevention, unfavorable emergency immunization of large-scale population, multiple immunizations, etc.

Active Publication Date: 2017-09-22
INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

Method used

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

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Embodiment 1

[0040] Example 1: Preparation of Zika virus disease vaccine with human replication defective adenovirus as carrier

[0041] 1. Optimization and synthesis of ZIKV prM endogenous signal peptide codon sequence, prM protein codon sequence and Env protein codon sequence.

[0042] Using the software Upgene (Gao, W., Rzewski, A., Sun, H., Robbins, P.D., & Gambotto, A. (2004). UpGene: Application of a web-based DNA codon optimization algorithm. Biotechnol Prog, 20 (2) , 443-448.doi:10.1021 / bp0300467) for the ZIKV prM endogenous signal peptide codon sequence and prM protein codon sequence of the ZIKV strain MRS_OPY_Martinique_PaRi_2015 (GeneBank Accession No KU647676) isolated during the Martinique outbreak in the Caribbean in 2015 And Env protein codon sequence is optimized to make it more suitable for expression in mammalian cells. The optimized codon sequence of the ZIKV prM endogenous signal peptide is shown in SEQ ID NO.3, and the oligonucleotide fragments are synthesized accordi...

Embodiment 2

[0100] Example 2 Immunological evaluation of Zika virus disease vaccine on mouse model.

[0101] In the mouse model, the immunization dose of the recombinant adenovirus vector ZIKV vaccine was studied, and the level of humoral immunity and cellular immunity induced by the vaccine was evaluated.

[0102] 1. Evaluation and comparison of humoral immune response induced by recombinant adenovirus vector ZIKV vaccine Ad5-Env and Ad5-Sig-prM-Env

[0103] 1.1 Comparison of vaccine immunization doses and evaluation of humoral immune response in mice

[0104] SPF grade female BALB / c mice (4-6 weeks old) were purchased from Victoria Levar. They were kept in the animal room of Fengtai Institute of Military Medical Sciences. The injection volume was 50 μl, blood was collected every week after immunization, and the prepared serum was frozen and stored at -20°C for future use. The mouse grouping, immunization dose and immunization site are shown in Table 2-4: Table 2: Ad5-Env immunization...

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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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/40C12N15/861C12N7/01A61K39/12A61P31/14
CPCA61K39/12C07K14/005C12N7/00C12N15/86C12N2710/10343C12N2710/10351C12N2770/24122C12N2770/24134C12N2770/24151C12N2800/22Y02A50/30
Inventor 陈薇郭强侯利华吴诗坡宋小红付玲王步森张金龙
Owner INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
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