Malaria vaccine
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Publication Number
US-9512190-B2
Publication Date
2016-12-06
Expiration Date
Abstract
The present invention provides a particle comprising a polypeptide and at least one malaria antigen, and a composition or vaccine comprising thereof, its use in medicine, particularly in the prevention or treatment of malaria infections.
Core Innovation
The invention concerns self-assembled virus-like particles comprising Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV) structural polypeptides fused or linked with a malaria antigen. The malaria antigen is a circumsporozoite protein (CSP) antigen containing circumsporozoite protein repeat epitopes such as NPNA and T-cell epitopes such as EYLNKIQNSLSTEWSPCSVT. The resulting virus-like particles present the malaria antigen as part of a fusion protein within a CHIKV or VEEV structural envelope context.
The malaria antigen is conjugated via defined attachment sites, including linker or fusion protein insertion into specific E2 residue-position sites. In the CHIKV case, insertion occurs at sites corresponding in position to sites between residues 509–512, 519–520, 529–530, or 531–532 of SEQ ID NO: 1 or 2; in the VEEV case, insertion occurs at sites corresponding in position to sites between residues 515–520 or 536–539 of SEQ ID NO: 3. The malaria antigens are selected as (NPNA)n repeats with n from 4 to 30 or as EYLNKIQNSLSTEWSPCSVT repeat segments with y from 1 to 6.
The invention further provides vaccine compositions and kits incorporating the CHIKV or VEEV virus-like particles, optionally with adjuvants, and also nucleic acids encoding the virus-like particles. The document states that immunization can induce antibodies against malaria antigens and can be used for treating and/or preventing malaria. Example data are described showing induction of high anti-CSP titers and partial protection after immunization with CHIKV-VLP and VEEV-VLP, with and without adjuvant, including studies in non-human primates and mice.
Claims Coverage
The independent claims cover two main subject matters: (i) CHIKV or VEEV virus-like particles engineered with at least one malaria antigen inserted into an E2 envelope protein at specified residue-position sites, where the inserted antigen is selected from defined NPNA and EYLNKIQNSLSTEWSPCSVT repeat forms; and (ii) isolated nucleic acids defined by sequence identity of 90% or more relative to multiple specified reference sequences (SEQ ID Nos. 26–27, 29–30, 32–33, 35–36, 38, 40, or 42).
Engineered CHIKV or VEEV virus-like particle with E2-inserted malaria antigen fusion protein
A CHIKV or VEEV virus-like particle contains at least one malaria antigen inserted into an E2 envelope protein to form a fusion protein, where the malaria antigen insertion occurs at CHIKV E2 sites corresponding in position to sites between residues 509–512, 519–520, 529–530, or 531–532 of SEQ ID NO: 1 or 2, or at VEEV E2 sites corresponding in position to sites between residues 515–520 or 536–539 of SEQ ID NO: 3.
Malaria antigen selection as defined NPNA repeats or EYLNKIQNSLSTEWSPCSVT repeat segments
The inserted malaria antigen is selected from (NPNA)n, where n is from 4 to 30, or (EYLNKIQNSLSTEWSPCSVT)y, where y is from 1 to 6.
Isolated nucleic acid defined by sequence identity to specified SEQ ID references
An isolated nucleic acid molecule consists of a nucleotide sequence having a sequence identity of 90% or more with a nucleotide sequence represented by SEQ ID Nos. 26–27, 29–30, 32–33, 35–36, 38, 40 or 42.
Overall, the claim coverage centers on virus-like particles presenting CSP-derived malaria antigens via defined insertion into E2 envelope proteins at specified residue-position sites, with antigen forms limited to (NPNA)n and (EYLNKIQNSLSTEWSPCSVT)y. A separate independent claim defines isolated nucleic acids by 90% or greater identity to multiple specified reference sequences.
Stated Advantages
Induction of high anti-CSP titers after immunization with CHIKV-VLP and VEEV-VLP, with and without adjuvant.
Partial protection after immunization with CHIKV-VLP and VEEV-VLP, with and without adjuvant.
Use for inducing antibodies and for treating and/or preventing malaria.
Documented Applications
Immunization to induce antibodies against malaria antigens, including CSP-derived targets.
Use for treating and/or preventing malaria.
Non-human primate studies reporting immunogenicity and partial protection after immunization with CHIKV-VLP and VEEV-VLP.
Mouse studies reporting immunogenicity and partial protection after immunization with CHIKV-VLP and VEEV-VLP, with and without adjuvant.
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