Multiple malaria pre-erythrocytic antigens and their use in the elicitation of a protective immune response in a host

An antigen, plasmodium technology, applied in the field of plasmodium antigenic peptides, can solve the problem that the attempt of protective antigen has not been suitable and so on

Pending Publication Date: 2019-12-17
INST PASTEUR +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

To date, despite the screening of thousands of PE peptides, mini-genes and gene 8-10 , but attempts to identify new protective antigens from live attenuated sporozoites have not yielded suitable candidates

Method used

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  • Multiple malaria pre-erythrocytic antigens and their use in the elicitation of a protective immune response in a host
  • Multiple malaria pre-erythrocytic antigens and their use in the elicitation of a protective immune response in a host
  • Multiple malaria pre-erythrocytic antigens and their use in the elicitation of a protective immune response in a host

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Embodiment

[0234] To address the complex problem of identifying protective antigens, the inventors designed a functional screen to identify and assemble novel PE protective antigens using a rodent malaria model in which mice (C57BL / 6) are resistant to Plasmodium berghei ( Pb) Sporozoite infection is extremely sensitive. In this model, the bactericidal protection induced by live irradiated sporozoites was mediated by antibodies and was mainly mediated by CD8 T cell responses against sporozoites and infrared phases, respectively. The inventors' screening strategy was designed based on four main features: i) parametric selection of 55 PE antigens based on abundance, orthology, predicted topology, and function; ii) synthesis of codon-optimized antigens to avoid enrichment Plasmodium sequences of AT and maximized expression in mammalian cells; iii) immunization with HIV-based lentiviral vectors that elicit strong humoral and cellular responses 11,12 and iv) measuring protection after severe ...

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Abstract

The invention relates to Plasmodium antigenic polypeptides identified through the use of a specifically devised functional immunization screening assay. In particular, the invention relates to antigenic polypeptides of malaria parasites wherein said antigenic polypeptides that exhibit a protective effect, especially that of eliciting a protective immune response in a host against challenge by Plasmodium sporozoites. The invention relates to a combination of compounds, comprising at least 2 distinct active ingredients wherein each active ingredient consists of an antigenic polypeptide of a Plasmodium parasite, a polynucleotide encoding the antigenic polypeptide, or a vector, in particular a viral vector, especially a lentiviral vector, expressing such antigenic polypeptide of a Plasmodium parasite, wherein one antigenic polypeptide is the circumsporozoite protein (CSP) or a polypeptidic derivative thereof and another antigenic polypeptide is either protein Ag40 (11-09) or protein Ag45 (11-10).

Description

technical field [0001] The present invention relates to Plasmodium antigenic polypeptides identified using a specially designed functional immunization screening assay. In particular, the present invention relates to an antigenic polypeptide of malaria parasite, wherein said antigenic polypeptide exhibits a protective effect in the host against challenge by malaria parasite sporozoites, in particular elicits a protective immune response. Thus, such identified antigenic polypeptides may constitute active ingredients suitable for the design of candidate vaccines, especially vaccines suitable for human hosts. Background technique [0002] Over the past 15 years, malaria control efforts have reduced global deaths from this mosquito-borne disease by 48%. Despite the marked decline in mortality, WHO estimates that there were about 215 million clinical episodes of malaria, resulting in more than 400,000 deaths in 2015. Practical malaria control programs rely heavily on the use of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/015C07K14/445
CPCA61K39/015C07K14/445A61K2039/70A61P33/06Y02A50/30C12N2740/15043A61K2039/5256C12N7/00C12N15/86
Inventor R·阿米诺P·沙尔诺A-S·贝尼翁C·布兰克
Owner INST PASTEUR
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