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Zika/dengue vaccine and application thereof

A vaccine, Zika virus technology, applied in the direction of vaccine, DNA/RNA vaccination, immunoassay, etc., can solve the problems of easy to cause ADE reaction, low neutralization activity, etc.

Active Publication Date: 2021-01-08
INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of them have low neutralizing activity, which is easy to cause ADE reaction, and most of the antibodies with high neutralizing activity are bound to other epitopes of E protein

Method used

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  • Zika/dengue vaccine and application thereof
  • Zika/dengue vaccine and application thereof
  • Zika/dengue vaccine and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0131] Example 1 Detection of humoral immune response in mice induced by ZIKV wild-type M / E and prM / E antigen-constructed recombinant chimpanzee adenovirus vaccine

[0132] The M / E antigen of the ZIKV FSS13025 virus strain (GenBank: JN860885.1) was constructed into a type 7 chimpanzee adenovirus vector, and the recombinant adenovirus vaccine AdC7-M / E-WT (recombinant adenovirus The construction of the vaccine AdC7-M / E-WT refers to: Xu et al. (2018) Journal of virology.vol.92, 6e01722-17.26Feb.), experiments have proved that it has a good protective effect on mice. It has been reported in the literature that the adenovirus vaccine constructed with the ZIKV prM / E antigen also has a protective effect. Therefore, the prM / E antigen of the ZIKV-SMGC-1 strain was constructed into a type 7 chimpanzee adenovirus vector, and the recombinant adenovirus AdC7- prM / E-WT (the construction of recombinant adenovirus AdC7-prM / E-WT refers to Hassan, Ahmed O et al. (2019) Cell reports, vol.28, 10:...

Embodiment 2

[0137] Example 2 In vitro experiments to detect the ADE of wild-type recombinant adenovirus vaccine AdC7-M / E-WT and AdC7-prM / E-WT immunized mice's serum to DENV

[0138] Since the fusion loop (FL) sequence of the envelop (E) protein of flaviviruses is very conserved, infection with ZIKV or immunization with vaccines expressing ZIKV E protein can induce the production of antibodies that cross-react with DENV, resulting in an antibody-dependent enhanced response to DENV ( Antibody-dependent enhancement, ADE) (Stettler, K., et al. (2016) Science: science.aaf8505.). Therefore, whether the sera of mice immunized with the recombinant adenovirus vaccines AdC7-M / E-WT and AdC7-prM / E-WT constructed above can produce ADE against DENV was tested.

[0139] Serum was serially diluted with RPMI-1640 medium (Invitrogen, C11875500BT) containing 1% FBS (taken from mice immunized with recombinant adenovirus vaccine in Example 1), and the diluted sample was added to a 96-well plate, 10 μl per wel...

Embodiment 3

[0142] Example 3 In vitro experiments to detect the ADE of monoclonal antibodies to DENV1-4

[0143]Z6 antibody is a monoclonal antibody that binds to ZIKV E protein after recombinant expression and purification of B cells isolated from the blood of a patient with ZIKV infection. Previous experiments have proved that it mainly binds to the FL epitope of ZIKV E protein (Wang, Qihui, et al.Science translational medicine8.369(2016):369ra179.), because the FL sequences of ZIKV and DENV are very conserved, and the Z6 antibody has low neutralizing activity (Wang, Qihui, et al.Science translational medicine8.369(2016):369ra179.), it is speculated that the Z6 antibody is likely to cause ADE to DENV, and the recombinant chimpanzee adenovirus vaccine AdC7-M / E-WT constructed using ZIKV wild-type M / E and prM / E antigens and AdC7-prM / E-WT are likely to activate the production of antibodies targeting the FL epitope, leading to ADE.

[0144] Whether the Z6 antibody pair will produce ADE effe...

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Abstract

An embodiment of the invention relates to the technical field of biology, in particular to a Zika / dengue vaccine and application thereof. The invention obtains epitope information of a main antibody causing an ADE effect based on crystal structure analysis and analysis of other structures and functions. According to an antigen provided by the embodiment of the invention, mutation is introduced into an E protein FL fusion region of a Zika virus or a dengue virus, and the antigen with the mutation cannot be combined with an antibody (FLE antibody) causing ADE. According to the vaccine obtained based on the antigen provided by the invention, after immunizing, generation of an FL epitope-induced antibody can be avoided, so that the ADE effect is reduced or eliminated.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a Zika / dengue vaccine and its application. Background technique [0002] Zika virus (ZIKV) is a mosquito-borne virus belonging to the Flaviviridae family. From 2015 to 2016, the ZIKV outbreak in the Americas spread to 84 countries around the world, including China. But so far no vaccine or drug is available. Although the incidence of ZIKV infection in the world has now weakened, ZIKV still poses a threat to people living in endemic areas, so the development of a vaccine for ZIKV is urgent. [0003] DENV virus (dengue virus, DENV) has 4 serotypes and is also a mosquito-borne virus belonging to the Flaviviridae family. [0004] The structure of ZIKV virus and DENV virus is relatively similar. They both have an icosahedral spherical structure with a capsule. The surface of the capsule contains an envelope (E) protein. The internal viral genome is a single-stranded positive-strand RNA...

Claims

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Application Information

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IPC IPC(8): C07K14/18A61K39/12A61P31/14G01N33/68G01N33/569
CPCC07K14/005A61K39/12A61P31/14G01N33/6854G01N33/56983C12N2770/24122C12N2770/24134A61K2039/53G01N2333/185G01N2469/20Y02A50/30A61K2039/5256C12N2710/10343A61K2039/575C07K16/1081C07K2317/34C07K2317/33C07K2317/70C07K2317/76C12N15/86C12Q1/701G01N2333/183A61P31/12C12Q1/70A61K2039/5254C12N7/00C12N2710/10334
Inventor 高福戴连攀严景华徐坤韩雨旋王奇慧黄庆瑞李金和
Owner INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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