Circumsporozoite proteins with increased expression in mammalian cells
AssigneeFred Hutchinson Cancer Center
InventorsMarie Pancera, Connor Weidle
Life of this patent
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Abstract
Mutated and/or truncated malarial circumsporozoite proteins (CSP) and associated nucleic acids that are more stable and highly expressed in mammalian cells are described. The mutated and/or truncated CSP and associated nucleic acids can be expressed to produce malaria vaccine antigens.
Claims20
A mutant N-terminus domain (NTD) of a circumsporozoite protein (CSP) comprising
- i) a KKNSR (SEQ ID NO:
- 1) to SSNSS (SEQ ID NO:
- 2) mutation directly upstream of a SLGENDD (SEQ ID NO:
- 3) cleavage site of a wild-type Plasmodium falciparum CSP;
- or
- ii) a KKNSR (SEQ ID NO:
- 1) to SSNSA (SEQ ID NO:
- 4) mutation directly upstream of a SLGENDD (SEQ ID NO:
- 3) cleavage site of a wild-type Plasmodium falciparum CSP;
- wherein the wild-type Plasmodium falciparum CSP comprises a sequence as set forth in SEQ ID NOs:
- 7, 10, or 19.
A circumsporozoite protein (CSP) comprising
- i) a KKNSR (SEQ ID NO:
- 1) to SSNSS (SEQ ID NO:
- 2) mutation directly upstream of a SLGENDD (SEQ ID NO:
- 3) cleavage site within the N-terminal domain of a wild-type Plasmodium falciparum CSP;
- or
- ii) a KKNSR (SEQ ID NO:
- 1) to SSNSA (SEQ ID NO:
- 4) mutation directly upstream of a SLGENDD (SEQ ID NO:
- 3) cleavage site within the N-terminal domain of a wild-type Plasmodium falciparum CSP;
- wherein the wild-type Plasmodium falciparum CSP comprises a sequence as set forth in SEQ ID NOs:
- 7, 10, or 19.
A method of stimulating an anti-malarial immune response in a subject comprising administering a therapeutically effective amount of a circumsporozoite protein (CSP) to the subject, wherein the CSP protein comprises
- ii) a KKNSR (SEQ ID NO:
- 1) to SSNSS (SEQ ID NO:
- 2) mutation directly upstream of a SLGENDD (SEQ ID NO:
- 3) cleavage site in the N-terminal domain (NTD) of a wild-type Plasmodium falciparum CSP;
- or
- iii) a KKNSR (SEQ ID NO:
- 1) to SSNSA (SEQ ID NO:
- 4) mutation directly upstream of a SLGENDD (SEQ ID NO:
- 3) cleavage site in the NTD of a wild-type Plasmodium falciparum CSP;
- wherein the wild-type Plasmodium falciparum CSP comprises a sequence as set forth in SEQ ID NOs:
- 7, 10, or 19, thereby stimulating the anti-malarial immune response in the subject.
Dependencies are inferred from the claim text.