Recombinantly expressed plasmodium CelTOS antigen and methods of use thereof
Inventors
Angov, Evelina • Bergmann-Leitner, Elke • Ockenhouse, Christian
Assignees
United States Department of the Army
Publication Number
US-9683024-B2
Publication Date
2017-06-20
Expiration Date
2029-11-23
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Abstract
A synthetic nucleotide, which transcribes as the cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen of Malaria Plasmodium, and methods of use thereof.
Core Innovation
The invention relates to a synthetic nucleotide sequence encoding the Plasmodium cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen of malaria, and methods of use thereof. It focuses on the manufacture and use of a vaccine incorporating recombinantly expressed Plasmodium CelTOS to induce pre-erythrocytic immunity against malaria.
Malaria remains a highly prevalent and often lethal parasitic infection, especially in tropical and subtropical regions. The disease is complicated by drug-resistant parasites and insecticide-resistant vectors. Immune responses target specific parasite stages, but current vaccines fail to induce long-lasting memory immunity. There is a need for an efficacious long-term pre-erythrocytic stage vaccine that can be used alone or with other treatments.
The invention provides immunization with CelTOS vaccines to mimic natural immunity development. Vaccination aims to reduce or stop sporozoite traversal through host cells required for liver infection, thereby protecting against infection or reducing disease severity. This effect is mediated by antibodies binding parasite surface proteins and blocking sporozoite motility and cell invasion, lowering parasite amplification in the liver.
Claims Coverage
The patent contains multiple claims that focus on the synthetic CelTOS polypeptide, its use in immunogenic compositions and vaccines, and methods related to immune induction and detection of malaria antibodies. There are seven independent inventive features identified.
Synthetic CelTOS polypeptide encoded by a specific synthetic nucleotide sequence
A synthetic CelTOS polypeptide, encoded by the synthetic nucleotide sequence identified as SEQ ID NO:1, representing a codon-harmonized sequence optimized for expression.
Immunogenic composition comprising the synthetic CelTOS polypeptide
An immunogenic composition that includes the synthetic CelTOS polypeptide to induce an immune response against malaria.
Recombinant expression of the synthetic CelTOS polypeptide without post-translational N-glycosylation
The synthetic CelTOS protein is recombinantly expressed in a system such as E. coli, resulting in the protein lacking post-translational N-glycosylation modifications.
Malaria vaccine comprising the synthetic CelTOS polypeptide
A malaria vaccine that includes the synthetic CelTOS polypeptide to confer protective immunity.
Methods of inducing immune response by administration of synthetic CelTOS polypeptide
Methods for inducing an immune response to Plasmodium malaria by administering an effective amount of the synthetic CelTOS polypeptide composition to a mammal.
Methods for detecting malaria antibodies in biological samples using synthetic polypeptide
Methods and kits for detection of malaria antibodies in biological samples using the synthetic CelTOS polypeptide as a binding reagent and a detection means for antibody complexes.
Use of adjuvants in immunogenic compositions and vaccination methods
The immunogenic compositions and vaccines comprising the synthetic CelTOS polypeptide may further include adjuvants to enhance the immune response.
The claims cover the synthetic nucleotide and encoded CelTOS polypeptide, compositions and vaccines containing them, methods for inducing immunity and detecting antibodies, and the utility of adjuvants in these compositions and methods.
Stated Advantages
Vaccination with the CelTOS antigen reduces or blocks sporozoite traversal and hepatocyte infection, offering protection against malaria infection or reducing disease severity.
Recombinant expression of CelTOS in E. coli yields high levels of soluble, properly folded protein suitable for vaccine formulation.
The codon harmonization technique optimizes protein expression and avoids complications from N-glycosylation, which can alter protein folding and immune response.
The CelTOS vaccine can be used alone or in combination with other malaria vaccines or treatments to induce a broader immune response.
Documented Applications
Use of the synthetic CelTOS polypeptide as a vaccine antigen to induce pre-erythrocytic immunity against malaria infection in humans or animals.
Use of recombinant CelTOS protein expressed in E. coli for production of malaria vaccine formulations.
Methods for immunizing mammals with CelTOS-containing compositions to induce protective antibodies reactive against malarial sporozoites and ookinetes, preventing liver stage infection and transmission.
Use of CelTOS antigens as reagents for stimulating immune cells, evaluating antibody responses by ELISA, Luminex, or similar immunoassays.
Development of monoclonal antibodies against Plasmodium CelTOS for potential passive immunotherapy.
Use of CelTOS antigen for studying protein folding and structure.
Diagnostic applications involving detection of malaria antibodies in biological samples using the synthetic CelTOS polypeptide as a detection reagent.
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