Pharmaceutical compositions comprising attenuated Plasmodium sporozoites and glycolipid adjuvants
Inventors
CHAKRAVARTY, Sumana • Hoffman, Stephen L. • Tsuji, Moriya
Assignees
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Publication Number
US-9642909-B2
Publication Date
2017-05-09
Expiration Date
Abstract
Disclosed herein are pharmaceutical compositions comprising Plasmodium sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range Plasmodium and analogues of α-galactosylceramide (α-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided.
Core Innovation
The invention relates to malaria-preventive pharmaceutical compositions and methods that reduce the risk of malaria in a human host exposed to pathogenic Plasmodium species parasites. The compositions include one or more species of live attenuated Plasmodium sporozoite-stage parasites and an excipient, and are administered prior to exposure.
The pharmaceutical composition is co-administered with a glycolipid adjuvant represented by the structure of formula 1, including α-GalCer analogues such as 7DW8-5, which is described as an NKT-cell ligand involving CD1d and iNKT cells. The disclosure states that the glycolipid adjuvant enables dose-/sporozoite-sparing and supports parenteral vaccination regimens, including non-IV routes.
The disclosure further includes co-administration regimens in which the glycolipid adjuvant and the live attenuated sporozoite-stage parasites are administered concurrently or sequentially, and may include optional overlap with antimalarial drug prophylaxis. Experimental evidence in BALB/c mice is described showing that adding 7DW8-5 to radiation-attenuated P. yoelii sporozoites increases protective rates and sustains protection upon rechallenge compared with sporozoites alone or adjuvant alone.
Claims Coverage
The independent claim covers a prophylactic method that reduces the risk of malaria in a human host by pre-exposure administration of a live attenuated Plasmodium sporozoite-stage parasite pharmaceutical composition co-administered with a glycolipid adjuvant of formula 1, specifically defined by a structure and R-group definition. The main inventive coverage is the combination of live attenuated sporozoites with a formula 1 glycolipid adjuvant in a co-administration framework prior to exposure.
Pre-exposure malaria risk reduction with live attenuated sporozoite-stage parasites plus excipient
A method of reducing the risk of malaria in a human host exposed to pathogenic Plasmodium species parasites, comprising administration of one or more doses of a pharmaceutical composition to said host prior to said exposure; wherein said pharmaceutical composition comprises one or more species of live attenuated Plasmodium sporozoite-stage parasites and an excipient.
Co-administration with glycolipid adjuvant of formula 1 defined by R-group
The pharmaceutical composition is co-administered with a glycolipid adjuvant represented by the structure of formula 1, wherein R is R′(CH2)10Ph(p-F).
The claim coverage centers on reducing malaria risk before exposure by administering one or more doses of a pharmaceutical composition containing live attenuated Plasmodium sporozoite-stage parasites and an excipient, where the composition is co-administered with a glycolipid adjuvant defined by formula 1 with a specified R-group.
Stated Advantages
Enables dose-/sporozoite-sparing.
Supports parenteral vaccination regimens, including non-IV vaccination regimens.
Increases protective rates.
Sustains protection upon rechallenge.
Documented Applications
Malaria-preventive administration in a human host prior to exposure to pathogenic Plasmodium species parasites using live attenuated Plasmodium sporozoite-stage parasites with a glycolipid adjuvant.
Parenteral vaccination regimens including non-IV routes, with concurrent or sequential co-administration of the glycolipid adjuvant and the sporozoite-stage parasites.
Use of radiation-attenuated P. yoelii sporozoites with addition of 7DW8-5 in BALB/c mice to evaluate protective rates and rechallenge protection [procedural detail omitted for safety].
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