Purified plasmodium and vaccine compositions
Inventors
Sim, B. Kim Lee • Li, Minglin • Stafford, Richard E. • Hoffman, Stephen L.
Assignees
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Publication Number
US-10272146-B2
Publication Date
2019-04-30
Expiration Date
Abstract
Disclosed are substantially purified Plasmodium sporozoites and preparations of Plasmodium sporozoites substantially separated from attendant non-sporozoite material, where the preparations of Plasmodium sporozoites have increasing levels of purity. Vaccines and pharmaceutical compositions comprising purified Plasmodium sporozoites are likewise provided. Methods of purifying preparations of Plasmodium sporozoites are also provided.
Core Innovation
The invention relates to substantially purified Plasmodium sporozoite preparations in which the amount of attendant material is reduced to a defined quantitative threshold. The preparations include Plasmodium vivax sporozoites that are metabolically active and infectious, and the objective is to provide a purified sporozoite preparation comprising less than 85 nanograms of attendant material per 25,000 sporozoites.
A further aspect is that the purified preparations can comprise even lower levels of attendant material, including less than 15 nanograms or less than 1 nanogram per 25,000 sporozoites. The disclosure emphasizes removal of attendant non-sporozoite material to meet the stated purity thresholds while maintaining sporozoite viability, and the preparations may also be described as aseptic/sterile preparations.
The purified sporozoite preparations are associated with attenuation and safety characteristics in which, after infecting a host, attenuated sporozoites do not cause malaria disease pathology. Attenuation is described as being established by a heritable genetic alteration or gene mutation, or by radiation, chemical, or environmental exposure, and the disclosure further links preparation performance to potency assessment using PfLSA-1 expression in human hepatocyte culture.
Claims Coverage
The independent claim covers a purified Plasmodium vivax sporozoite preparation with defined purity and biological activity. Dependent claims add specific quantitative thresholds for attendant material, an aseptic preparation condition, and attenuation criteria tied to failure to cause malaria disease pathology, including multiple attenuation-establishing mechanisms.
Purified Plasmodium vivax sporozoite preparation with attendant material threshold
A purified preparation of Plasmodium-species sporozoites comprising less than 85 nanograms of attendant material per 25,000 sporozoites, wherein the sporozoites are metabolically active and infectious and the species is Plasmodium vivax.
Purified preparation with reduced attendant material below 15 ng
The purified preparation comprising less than 15 nanograms of attendant material per 25,000 sporozoites.
Purified attenuated sporozoites that do not cause malaria disease pathology
A purified preparation of attenuated sporozoites in which, after infecting a host, the attenuated sporozoites do not cause malaria disease pathology.
Purified attenuated sporozoites with attenuation established by genetic mutation or exposure
A purified preparation in which attenuation is established by introducing a heritable genetic alteration or gene mutation, or by radiation, chemical, or environmental exposure.
Purified preparation with reduced attendant material below 1 ng
A purified preparation containing less than 1 nanogram of attendant material per 25,000 sporozoites.
Across the independent and dependent claims, the core inventive theme is a purified, metabolically active, infectious Plasmodium vivax sporozoite preparation defined by quantitative attendant material limits, optionally in an aseptically prepared form. The claims further narrow embodiments to attenuated sporozoites that do not cause malaria disease pathology, with attenuation established via genetic alteration or various exposures, while maintaining the purified preparation framework.
Stated Advantages
Provides sporozoite preparations with reduced attendant material while maintaining metabolically active and infectious sporozoites.
Enables purity thresholds through reduction of attendant material to less than specified limits (e.g., <85 ng per 25,000 sporozoites and lower).
Supports safety through attenuated sporozoites that do not cause malaria disease pathology after infecting a host.
Supports potency assessment using PfLSA-1 expression in human hepatocyte culture.
Documented Applications
Vaccine compositions and pharmaceutical compositions for preventing malaria.
Challenge studies using purified pathogenic sporozoites as research/drug/vaccine challenge tools.
Use of purified preparations in potency assessment based on PfLSA-1 expression in human hepatocyte culture.
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