Malaria immunogen and methods for using same
Inventors
Chackerian, Bryce C. • Zavala, Fidel P. • Peabody, David S. • Petrovsky, Nikolai • Jelinkova, Lucie
Assignees
Vaxine Pty Ltd • VAXINE Pty Ltd • Johns Hopkins University • UNM Rainforest Innovations
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Publication Number
US-12121574-B2
Publication Date
2024-10-22
Expiration Date
Abstract
An immunogen useful for treating malaria generally includes an immunogenic carrier and an antigenic malaria circumsporozoite protein (CSP) peptide that includes the peptide NANPNVDPNANPNVD (SEQ ID NO:2) linked to the immunogenic carrier. The immunogen may be administered to a subject having or at risk of having malaria. Alternatively, the immunogen may be administered to an individual having or at risk of having Plasmodium falciparum blood stage parasitemia. In some cases, the immunogen can be administered in combination with another therapeutic agent for treating malaria of Plasmodium falciparum blood stage parasitemia.
Core Innovation
The invention relates to a malaria immunogen comprising an immunogenic carrier and an antigenic malaria circumsporozoite protein (CSP) junction region peptide. The immunogenic carrier comprises a Qβ bacteriophage virus-like particle (VLP), and the CSP junction region peptide comprises NANPNVDPNANPNVD (SEQ ID NO:2) linked to the immunogenic carrier.
The immunogen can include a second antigenic CSP peptide. The antigenic peptides can be displayed together on a single VLP, or can be displayed using different VLP populations, and linkage of the CSP peptide to the immunogenic carrier can use SMPH cross-linker (succinimidyl-6-[β-maleimidopropionamido]hexanoate).
Compositions and a vaccine can be provided that include the malaria immunogen, optionally with ADVAX-3/ADVAX adjuvant. The document also describes methods for treating or prophylactically administering the composition to subjects at risk of malaria or Plasmodium falciparum blood-stage parasitemia, including combination with additional therapeutic agents.
Claims Coverage
The provided claim set centers on one independent claim defining a malaria immunogen that links a Qβ bacteriophage VLP carrier to a specific CSP junction-region peptide sequence (SEQ ID NO:2). The summarized dependent claims add SMPH linkage, a second CSP peptide, antigen display on a single VLP, and downstream uses in compositions/vaccines and methods of treating or prophylactically administering to subjects for malaria, including Plasmodium falciparum blood-stage parasitemia.
Qβ bacteriophage VLP immunogenic carrier linked to CSP junction-region peptide
An immunogen comprises an immunogenic carrier comprising a Qβ bacteriophage virus-like particle (VLP) and an antigenic malaria CSP junction region peptide comprising NANPNVDPNANPNVD (SEQ ID NO:2) linked to the immunogenic carrier.
SMPH cross-linker linkage of CSP peptide to the carrier
The immunogen links the immunogenic carrier and the CSP junction region peptide using the succinimidyl-6-[β-maleimidopropionamido]hexanoate (SMPH) cross-linker molecule.
Second antigenic CSP peptide in the immunogen
The immunogen further comprises a second malaria circumsporozoite protein (CSP) peptide antigen.
Display of SEQ ID NO:2 and second CSP peptide on a single VLP
The immunogen displays SEQ ID NO:2 and the second antigenic CSP peptide on a single VLP.
Specific identity of the second antigenic CSP peptide
In the claimed method, the second antigenic CSP peptide consists of amino acids 21-35 of SEQ ID NO:1.
Pre-symptomatic prophylactic administration
In the claimed method, administering the composition is characterized by administering to an individual before any malaria symptoms or clinical signs appear.
Overall, the claims focus on the Qβ bacteriophage VLP-linked malaria CSP junction-region peptide comprising NANPNVDPNANPNVD (SEQ ID NO:2), with further limitations including SMPH linkage, a second CSP peptide, specified antigen display configurations, and administration before malaria symptoms or clinical signs. The provided claim summary also identifies application to Plasmodium falciparum blood-stage parasitemia.
Stated Advantages
Elicits durable anti-CSP antibodies.
Reduces liver parasite load.
Reduces blood-stage parasitemia in mouse challenge.
Documented Applications
Treating or prophylactically administering a composition to subjects at risk of malaria or Plasmodium falciparum blood-stage parasitemia, including combination with additional therapeutic agents.
Mouse challenge application comparing L9 VLPs (SEQ ID NO:2 epitope) to CIS43 VLPs and control VLPs, with outcomes including liver parasite load and blood-stage parasitemia.
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