HPV/Cyaa-based chimeric proteins and their use in inducing immune responses against HPV infection and HPV-induced disease

一种嵌合蛋白、蛋白的技术，应用在嵌合蛋白领域，能够解决无保护性细胞免疫应答、抗原细胞免疫应答弱等问题

CN104736173BInactive Publication Date: 2019-02-05DZHENTISEL
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Publication Date
2019-02-05
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention relates to a chimeric protein comprising or consisting of, from N-terminal to C-terminal, (a) a N-terminal part of a Bordetella CyaA protein (b) a heterologous polypeptide comprising antigens originating from different HPVs, and (c) a C-terminal part of a Bordetella CyaA protein. The invention also relates to a polynucleotide encoding this chimeric protein. A composition comprising at least one chimeric protein(s) of the invention and the prophylactic and / or therapeutic uses of said composition are also part of the invention.
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Description

technical field

[0001] The present invention relates to a chimeric protein comprising or consisting of: from N-terminus to C-terminus, (a) the N-terminal portion of the Bordetella CyaA protein; (b) a heterologous polypeptide, which Contains antigens from different HPVs; and (c) the C-terminal portion of the Bordetella CyaA protein. The present invention also relates to a polynucleotide encoding the chimeric protein. Another aspect of the present invention also relates to a composition comprising at least one chimeric protein of the present invention and the prophylactic and / or therapeutic use of said composition. Background technique

[0002] The adenylyl cyclase (CyaA) of the Bordetella type, specifically Bordetella pertussis, has been extensively described as a recombinant vector that efficiently delivers polypeptides such as antigens to antigen presentation In the cytosol of the cell (APC) [1]、[2]、[3] . In addition, recombinant CyaAs have been used to effectively trea...

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Embodiment Construction

[0352] I. Materials and methods

[0353] mouse

[0354] Six-week-old female C57BL / 6 mice (H-2 b ). Mice were housed under pathogen-free conditions with ad libitum access to water and food. Procedures involving animals and their care complied with Genticel guidelines, which adhere to national and international laws and policies, and were reviewed by local ethics committees.

[0355] For some of the HPV types used in the present invention, other mice with different genetic backgrounds can be advantageously used. Such mice can be purchased from Janvier Laboratories and include: DBA / 2JRi (H2K d / H2D d ), or CBA / JRi(H2K k / H2D k )SJL / JRi(H2K s / H2D s ) and FVB / NRi (H2K q / H2D q ).

[0356] Other mice, such as humanized mice, which have HLA, particularly the HLA-A2 haplotype, are also of interest in determining the immune response elicited by the constructs of the invention. Transgenic HLA-A2.1 mice can be purchased from TACONIC (USA) in mice expressing the human HLA-...