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Malaria vaccine

a technology for malaria and vaccines, applied in immunology disorders, antibody medical ingredients, fusion with rna-binding domains, etc., can solve the problems of falciparum /i>remaining a major public health threat, relatively few proteins have been studied for potential vaccine development, and the failure of the most poorly developed tropical countries

Inactive Publication Date: 2017-02-09
VLP THERAPEUTICS LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a particle that can be self-assembled, which contains a polypeptide and a malaria antigen. The polypeptide and malaria antigen are linked through specific attachment sites. Additionally, a nucleic acid molecule is provided that is designed to express the particle. The composition containing the particle and nucleic acid molecule can be used as a vaccine or for passive immunization against malaria. The particle can also be used to stimulate antibodies or immune responses against malaria antigens. Furthermore, the invention provides a method of presenting an antigen on a macrophage and a method for producing the particle.

Problems solved by technology

These were successful in the Southeast U.S. for example, but failed in most poorly developed tropical countries.
Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa.
Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development.
There are currently no licensed vaccines against malaria.
Many others are still restricted to small-scale fundamental research, despite their success in preclinical tests.
The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Chikungunya Virus (CHIKV) Like Particle Comprising a Virus Structural Polypeptide and a Fragment of Malaria Antigen

[0138]The following polynucleotides of malaria CSP1 proteins are used. N terminal linker is SGG and C terminal linker is GGS.

VLP74 (6 repeat of NPNA amino acid sequence)(SEQ ID No.: 46)Sggnpnanpnanpnanpnanpnanpnaggs(SEQ ID No.: 47)(Tccggaggaaacccgaatgccaatcccaacgcgaaccccaatgctaacccaaatgccaacccaaacgccaaccccaacgctggtggatcc)VLP78 (25 repeat of NPNA amino acid sequence)(SEQ ID No.: 48)Sggnpnanpnanpnanpnanpnanpnvdpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnaggs(SEQ ID No.: 49)(tccggaggaaacccgaatgccaatcccaacgcgaaccccaacgctaaccccaacgccaatccgaatgcaaacccgaacgttgacccaaacgccaacccgaatgccaatcccaacgcgaaccccaatgctaacccaaatgccaacccaaacgccaaccccaacgctaatccaaacgccaaccctaacgccaatcccaacgcgaatcctaacgctaatcccaacgcaaatcccaatgctaatccgaacgcgaaccctaatgcaaaccccaacgccaacccgaacgctaacccgaacgctaatcccaacgccggtggatcc)

[0139]The respective polynucleotides was ...

example 2

Preparation of Venezuelan Equine Encephalitis Virus (VEEV) Like Particle Comprising a Virus Structural Polypeptide and a Fragment of Malaria Antigen

[0142]The same polynucleotides of malaria CSP1 proteins (VLP74 and VLP78) used in EXAMPLE 1 are used. N terminal linker is SGG and C terminal linker is GGS.

[0143]The respective polynucleotides was inserted between the codons encoding Ser at 518-position and Ser at 519-position of SEQ ID Nos.19 or 20 (SEQ ID No.3) to construct a plasmid (hereinafter referred to as VEEV-VLP74 or 78) for expressing Venezuelan equine encephalitis virus like particle where the modified VLP74 or 78-derived peptide is inserted into E2 of Venezuelan equine encephalitis virus structural polypeptide.

[0144]293F cells (Lifetechnology) were transfected with the plasmid using PEI (GE Healthcare) or GeneX (ATCC). 4 days after the transfection, the conditioned medium was collected and centrifuged at 3000 rpm for 15 minutes to separate it from cells. The supernatant was ...

example 3

Immunogenicity in Non-Human Primate (Monkey)

[0146]The monkeys were immunized with ×25-CHI (80 ug) at 0 week and ×6-VEE (80 ug) at 3 week by intramuscular injection with or without adjuvant (Sigma Adjuvant System, Sigma, S6322). ×25-CHI means 25 times malaria CSP repeat amino acid NPNA on CHIKV VLP particle (VLP78_15). ×6-VEE means 6 times malaria CSP repeat amino acid NPNA on VEEV VLP particle (VLP74_25). The blood is taken at 2 and 5 weeks after the first immunization.

[0147]96 well ELISA plate were coated with 50 ng of Recombinant Circumsporozoite Protein (rCSP) (Reagent Proteins, ATG-422) in 100 ul PBS buffer pre well. The Plates after 2 hours incubation were washed three times TBS buffer containing 0.05% Tween-20 and blocked with TBS buffer containing 0.05% Tween-20 and 5% dry milk. The heat inactivated diluted serum from monkeys were added in the blocking buffer and incubated for 1 h at room temperature. After washing three times, peroxidase labeled goat anti-human IgG or anti-m...

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Abstract

The present invention provides a particle comprising a polypeptide and at least one malaria antigen, and a composition or vaccine comprising thereof, its use in medicine, particularly in the prevention or treatment of malaria infections.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This is a continuation of U.S. application Ser. No. 14 / 294,968 filed Jun. 3, 2014, which claims benefit from U.S. Provisional Application No. 61 / 830,436, filed Jun. 3, 2013, and U.S. Provisional Application No. 61 / 906,583, filed Nov. 20, 2013. The entire disclosures of the prior applications are considered part of the disclosure of the accompanying continuation, and are hereby incorporated by reference.TECHNICAL FIELD[0002]The present invention relates to a particle comprising a polypeptide and at least one malaria antigen, and a composition or vaccine comprising thereof, its use in medicine, particularly in the prevention or treatment of malaria.BACKGROUND[0003]Malaria is one of the world's most prevalent serious infectious diseases, with approximately 250 million cases and 1 million deaths per year (WHO, 2009). Mortality is primarily in children under the age of five and in pregnant women. Every 45 seconds, an African child dies of mala...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/015A61K39/193A61K39/12
CPCA61K39/015A61K39/12A61K2039/5258C12N2770/36123C12N2770/36134A61K39/193A61K38/162C07K14/445A61P33/02A61P33/06A61P37/04Y02A50/30A61K2300/00A61K35/68C12N2770/36143C07K14/00C07K14/005C07K2319/85C07K14/705C12N7/00A61K39/00C12N15/09C12N2770/36034
Inventor UENO, RYUJIAKAHATA, WATARU
Owner VLP THERAPEUTICS LLC
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