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AssigneeMedical Research Council
InventorsAnthony Holder, Berry Birdsall, James Feeney, William Morgan, Shabih Syed, Chairat Uthaipibull
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A non-naturally occurring variant of a C-terminal fragment of a Plasmodium merozoite surface protein-1 (MSP-1) wherein said variant has (i) a reduced affinity, compared with a naturally occurring Plasmodium MSP-119, for at least one first antibody capable of blocking the binding of a second antibody, which second antibody inhibits the proteolytic cleavage of Plasmodium MSP-142 and (ii) substantially the same affinity for at least one third antibody compared with said naturally occurring Plasmodium MSP-119. which third antibody inhibits the proteolytic cleavage of Plasmodium MSP-142 is provided for use in an anti-malarial vaccine.
A non-naturally occurring variant of a C-terminal fragment of a Plasmodium merozoite surface protein-1 (MSP-1) wherein said variant has (i) a reduced affinity, compared with a naturally occurring Plasmodium MSP-119, for at least one first antibody capable of blocking the binding of a second antibody, which second antibody inhibits the proteolytic cleavage of Plasmodium MSP-142 and (ii) substantially the same affinity for at least one third antibody compared with said naturally occurring Plasmodium MSP-119. which third antibody inhibits the proteolytic cleavage of Plasmodium MSP-142.
A non-naturally occurring variant of a C-terminal fragment of a Plasmodium merozoite surface protein-1 (MSP-1) comprising an amino acid modification at any one of amino acid residues 14, 15, 27, 31, 34, 43, 48 and 53 of the Plasmodium falciparum MSP-1 19 amino acid sequence shown as SEQ I.D. No. 1 or their equivalent positions in other Plasmodium MSP-119 polypeptides.
A method for producing a Plasmodium MSP-1 variant for use in preparing a vaccine composition which method comprises modifying one or more amino acid residues of a Plasmodium MSP-1 C-terminal fragment such that the resulting derivative has (i) a reduced affinity, compared with a naturally occurring Plasmodium MSP-119, for at least one first antibody capable of blocking the binding of a second antibody, which second antibody inhibits the proteolytic cleavage of Plasmodium MSP-142 and (ii) substantially the same affinity for at least one third antibody compared with said naturally occurring Plasmodium MSP-119, which third antibody inhibits the proteolytic cleavage of Plasmodium MSP-142.
A computer readable medium having stored thereon a model of the MSP-119 NMR structure.
A nucleic acid encoding a Plasmodium MSP-1 polypeptide, in which the nucleic acid is optimised for expression in a heterologous host cell.
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