Compositions and methods for regulation of chronic toxoplasma infection

Patent metadata

Field	Value
Publication number	US-11945845-B2
Application number	US-202017595894-A
Country	US
Kind code	B2
Filing date	May 30, 2020
Priority date	May 31, 2019
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

The present disclosure provides genetically altered protozoan parasites comprising a mutation in a bradyzoite formation deficient 1 (BFD1) gene, wherein the mutation inhibits differentiation of the parasite into a bradyzoite. The genetically altered protozoan parasites can be utilized in vaccine compositions and in methods of treating apicomplexan parasite infection.

First claim

What is claimed is:

1. A genetically altered Toxoplasma gondii comprising a mutation in a bradyzoite formation deficient 1 (BFD1) gene (SEQ ID NO:1), wherein the mutation is a deletion of all or a portion of the coding sequence of the BFD1 gene, and wherein the mutant BFD1 gene is defective in initiating differentiation of the Toxoplasma gondii into a bradyzoite.

2. The Toxoplasma gondii of claim 1 , wherein the mutation is a deletion of a portion of the coding sequence of the BFD1 gene.

3. The Toxoplasma gondii of claim 1 , wherein the mutation is a deletion of the entire coding sequence of the BFD1 gene.

4. The Toxoplasma gondii of claim 1 , wherein the mutation is a loss-of-function mutation.

5. The Toxoplasma gondii of claim 4 , wherein the loss-of-function mutation is a null mutation.

6. A vaccine composition comprising the Toxoplasma gondii of claim 1 and a pharmaceutically-acceptable carrier.

7. The vaccine composition of claim 6 , further comprising an adjuvant.

8. The vaccine composition of claim 6 , comprising a live vaccine.

9. The vaccine composition of claim 6 , wherein the Toxoplasma gondii expresses a heterologous antigen.

10. A method of inducing an immune response to Toxoplasma gondii in a subject in need thereof, comprising administering to the subject a vaccine composition comprising a genetically altered Toxoplasma gondii , wherein the Toxoplasma gondii comprises a mutation in a bradyzoite formation deficient 1 (BFD1) gene (SEQ ID NO:1), wherein the mutation is a deletion of all or a portion of the coding sequence of the BFD1 gene, and wherein the mutant BFD1 gene is defective in initiating differentiation of the Toxoplasma gondii into a bradyzoite.

11. The method of claim 10 , wherein the subject in need thereof is a human.

12. The method of claim 10 , wherein the subject in need thereof is a non-human mammal.

13. The method of claim 10 , wherein the subject in need thereof has an acute or chronic Toxoplasma gondii infection.

14. A method of delivering an antigen to a subject in need thereof, the method comprising administering the antigen to the subject a wherein the antigen is delivered in a genetically altered Toxoplasma gondii , wherein the Toxoplasma gondii comprises a mutation in a bradyzoite formation deficient 1 (BFD 1) gene (SEQ ID NO:1), wherein the mutation is a deletion of all or a portion of the coding sequence of the BFD 1 gene, and wherein the mutant BFD 1 gene is defective in initiating differentiation of the Toxoplasma gondii into a bradyzoite.

Assignees

• Whitehead Inst Biomedical Res

Inventors

• Waldman Ben
• Lourido Sebastian

Classifications

• C07K14/45 Primary

  Toxoplasma · CPC title

• A61K39/002

  Protozoa antigens · CPC title

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C12N1/10

  Protozoa; Culture media therefor · CPC title