Recombinant and synthetic DNA and encoded polypeptides based upon the natural sequences of the malaria-causing parasite Plasmodium vivax; particularly based upon the circumsporozoite protein of Pv, as well as vaccines which utilize these compositions; antimalaria agents

Inventors

Sim, Kim Lee • Hoffman, Stephen • Arevalo, Myriam • Herrera, Socrates

Assignees

Sanaria Inc

Abstract

Malaria in humans is caused by infection with Plasmodium species parasites including P. vivax. The biology and immunobilogy of P. vivax is distinct from that of P. falciparum. Provided are unique synthetic polypeptides and DNA molecules which encode them. Each of these molecules correspond to regions of the circumsporozoite protein of P. vivax. Each molecule comprises sequences corresponding to several repeats of the central region of the Pv 210 variant fused to sequences corresponding to several repeats of the central region of the Pv 247 variant. Each molecule additionally comprises sequences corresponding to either the amino terminus, the carboxy terminus, or both the amino and carboxy termini of the PvCSP. Also provided are vaccines comprising these unique sequences and methods of using these vaccines and sequences to prevent and treat Pv malaria.

Core Innovation

The invention relates to isolated DNA molecules and vaccine compositions based on Plasmodium vivax circumsporozoite protein (PvCSP), including synthetic/recombinant DNA and chimeric polypeptides. The DNA constructs and polypeptides include central repeat units derived from Pv210/common and Pv247/variant allelic variants, combined in tandem with N-terminus and/or C-terminus regions.

The described compositions include DNA molecules encoding PvCSP-based chimeric polypeptides and corresponding protein components. The compositions are presented as vaccine compositions for preventing and/or mitigating Plasmodium vivax malaria, including codon optimized genes and replicon delivery concepts.

The document also describes experimental characterization supporting the PvCSP-based constructs, including gene expression for codon optimized gene expression in Pichia pastoris, antigenicity measurements using human sera, and immunogenicity measurements in BALB/c mice for selected protein constructs. Functional evaluation includes inhibition of liver-stage development (ILSDA) in human hepatoma cells, and T-cell response characterization using IFN-gamma ELISpot.

Claims Coverage

The independent claim set focuses on isolated DNA molecules defined by specific nucleotide sequences (SEQ ID NOs: 2, 4, and 6), with dependent claim coverage narrowing to specific selected sequences and, in at least one dependent claim, to an isolated DNA molecule operatively linked in a replicon. Across the independent claim(s), the core inventive coverage is the sequence-defined isolated DNA molecule, optionally configured for replicon functionality.

Overall, the claim coverage centers on isolated DNA molecules specified by nucleotide sequence selection among SEQ ID NOs: 2, 4, and 6, with additional inventive coverage added by a functional replicon linkage in at least one dependent claim.

Stated Advantages

Documented Applications