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Toxoplasma gondii vaccines and their use

a technology of toxoplasma gondii and vaccines, which is applied in the field of intracellular parasites, can solve the problems of toxic or hypersensitivity, inability to eliminate latent parasites, and cyst forms that cannot be eliminated

Inactive Publication Date: 2019-09-19
MASSACHUSETTS INST OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides a chimeric polypeptide that combines different peptide domains to create a multi-functional molecule. The polypeptide can be used to treat or prevent infections caused by Toxoplasma gondii, a parasite that can cause damage to the brain and other organs. The polypeptide is made up of two parts: a CD8+ T cell domain and a CD4+ T cell domain. The CD8+ T cell domain is made up of multiple peptides that are specific to Toxoplasma gondii, while the CD4+ T cell domain is made up of peptides that are more broadly reactive. The chimeric polypeptide can be administered as a pharmaceutical composition or as a vaccine to protect against the parasite. The invention also provides methods for using the chimeric polypeptide to treat or prevent Toxoplasma gondii infection.

Problems solved by technology

Although antiparasitic medicines such as sulfadiazine and pyrimethamine are effective against tachyzoites, they are associated with toxicity or hypersensitivity and do not eliminate the latent, cyst form of the parasite.

Method used

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  • Toxoplasma gondii vaccines and their use
  • Toxoplasma gondii vaccines and their use
  • Toxoplasma gondii vaccines and their use

Examples

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Effect test

example 1

Adjuvanted Multi-Epitope Vaccines Protect HLA-A*1101 Transgenic Mice Against Toxoplasma Gondii

[0076]We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE)) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included five of down selected CD8+ T cell eliciting epitopes, a universal CD4+ helper T lymphocyte epitope (PADRE), a secretory signal, all arranged to maximize MHC Class I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*1101 transgenic mice. These multi-epitope vaccines increased memory CD8+T cells that produced IFN-γ and protected mice against parasite burden when challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross presentation of the antigens may account for the immunogenicity of our adjuvanted protein. This work demonstrates a novel a...

example 2

Novel Protein Nanovaccine Confers Robust Immunity Against Toxoplasma

[0110]We designed and produced a self-assembling protein nanoparticle (SAPN) containing five CD8+ HLA-A03-11 supertypes restricted epitopes from antigens expressed during Toxoplasma's lifecycle, PADRE which is a CD4+ T cell, universal epitope, and flagellin as scaffold and TLR5 agonist. These epitopes were separated by N / KAAA (SEQ ID NO: 21 & 22) spacers and optimized for proteasomal cleavage. SAPN-GLA-SE was evaluated for its efficacy in inducing IFN-γ and protection against T. gondii in mice with an HLA-A*1101 transgene. In our data, immunization with SAPN adjuvanted with TLR4 ligand-emulsion (GLA-SE), activated CD8+ T cells to produce IFN-γ. SAPN-GLA-SE also protected against subsequent challenge with type II parasites in mice with an HLA-A*1101 transgene. Hence, combining CD8+ T cell-eliciting peptides and PADRE into a multi-epitope within a single self-assembling protein, administered with adjuvant GLA-SE, lea...

example 3

Novel, Immunogenic, Self-Replicating RNA Nanoparticle, Platform Encoding Immunosense Designed Toxoplasma Peptides is A Vaccine That Protects HLA-A*1101 Transgenic Mice

[0133]We designed and produced a self-replicating RNA nanoparticle displaying peptide epitopes that induces protective CD8+ and CD4+ T cells against T. gondii infection. These RNA replicons are composed of Venezuelan Equine Encephalitis (VEE) alphavirus backbone, 5 CD8+ HLA-A03-1101 supertype-restricted epitopes from antigens expressed during the life cycle of Toxoplasma, and a universal CD4+ T cell epitope (PADRE). All are encapsulated in lipid nanoparticles and evaluated for their immunogenic and protective potential against T. gondii in HLA-A*1101 transgenic mice. Administered without the need for an adjuvant, the self-replicon nanoparticles elicit T cells producing IFN-γ and protect mice against parasite burden when challenged with type II T. gondii strain. Thus, this work demonstrates that RNA replicon nanoparticl...

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Abstract

Disclosed herein are polynucleotides encoding multi-epitope polypeptides and assemblies thereof, and their use for treating or limiting Toxoplasma gondii infection.

Description

CROSS REFERENCE[0001]This application claims priority to U.S. Provisional Patent Application Ser. No. 62 / 324,225 filed Apr. 18, 2016, incorporated by reference herein in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH[0002]This invention was made with U.S. government support under grant numbers DMID-NIAID U01 AI77887, R01 27530, and U19 A1110819, all awarded by The National Institutes of Health. The U.S. Government has certain rights in the invention.BACKGROUND[0003]Toxoplasma gondii is an intracellular parasite that can cause severe ocular and neurological diseases in fetuses, newborn infants, and immunocompromised individuals (1). The acute infection is characterized by proliferation of tachyzoites, which replicate rapidly within host cells and lyse their host cells within 24-48 hours to release large numbers of progeny. In response to immune pressure, the parasite differentiates into a slow-growing form called bradyzoites, which resides within intracellular cysts. F...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/002A61K9/00A61P33/02
CPCA61K39/002A61P33/02A61K9/0009A61K9/0019A61K39/012A61K2039/55566A61K2039/57A61K2039/70C07K2319/00A61P37/04
Inventor MCLEOD, RIMAEL BISSATI, KAMALZHOU, YINGALEXANDER, JEFFVANG, LOREED, STEVEPAULILLO, SARA M.RAMAN, SENTHIL K.BURKHARD, PETERMELO, MARIANEIRVINE, DARRELWEISS, RONZHANG, YUANSETTE, ALESSANDROSIDNEY, JOHNLIVINGSTON, BRIAN D.LORENZI, HERNAN
Owner MASSACHUSETTS INST OF TECH
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