Malaria vaccine
Inventors
Kumar, Nirbhay • Angov, Evelina
Assignees
Johns Hopkins University • United States Department of the Army • US Army Medical Research and Development Command
Publication Number
US-8501926-B2
Publication Date
2013-08-06
Expiration Date
2029-07-22
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Abstract
The present invention features immunogenic compositions based on pre-fertilization or post-fertilization antigens expressed in the circulating gametocytes in the peripheral blood of infected persons or on the malaria parastes' stages of development in the mosquito midgut including extracellular male and female gametes, fertilized zygote and ookinete. The invention also features methods to prevent the transmission of malaria using the immunogenic compositions of the invention.
Core Innovation
The invention features immunogenic compositions based on pre-fertilization or post-fertilization antigens expressed in circulating gametocytes in the peripheral blood of infected persons or on malaria parasite stages of development in the mosquito midgut, including extracellular male and female gametes, fertilized zygote, and ookinete. It also encompasses methods to prevent the transmission of malaria by administering these immunogenic compositions.
The invention addresses problems in malaria control, notably that malaria remains a severe infectious disease with approximately 300 million affected globally, primarily caused by Plasmodium falciparum and P. vivax. Existing efforts like insecticide-treated nets and combination drugs face challenges due to drug resistance, emphasizing the need for a safe and effective malaria vaccine. Prior vaccine efforts have focused on pre-erythrocytic, erythrocytic, and sexual parasite stages, with some partial success but no fully effective solution.
A key innovation is the use of an approach termed 'codon harmonization' that aligns the codon usage frequency of the target gene with that of the host expression system, enabling heterologous expression of the parasite proteins in correct conformation and sufficient quantities. The invention successfully applies this to express full-length Pfs48/45, a pre-fertilization antigen, in Escherichia coli with high yield and proper folding, which has been challenging previously. The recombinant protein elicits potent malaria transmission blocking antibodies in both mice and non-human primates (olive baboons). The invention further discloses methods of immunization and treatment using immunogenic compositions comprising one or more Plasmodium falciparum or Plasmodium vivax pre-fertilization or post-fertilization antigens, derived from codon harmonized genes, capable of blocking malaria transmission and preventing disease.
Claims Coverage
The patent claims include a total of five inventive features covering methods, sequences, vectors, cells, and kits related to codon harmonized malaria antigens and their use.
Method for preparing codon harmonized Pfs48/45 antigen sequence
A method comprising determining codon usage frequency of the native Pfs48/45 gene (SEQ ID NO: 7) and substituting codons with those of similar frequency from a host cell to prepare a codon harmonized Pfs48/45 nucleotide sequence (SEQ ID NO: 2).
Isolated codon harmonized nucleotide sequence
An isolated codon harmonized nucleotide sequence comprising SEQ ID NO: 2 prepared by the codon harmonization method.
Vector comprising codon harmonized Pfs48/45 sequence
A vector containing the codon harmonized Pfs48/45 nucleotide sequence (SEQ ID NO: 2) suitable for expression in a cell.
Cell expressing codon harmonized Pfs48/45 vector
A cell transformed to express the vector comprising the codon harmonized Pfs48/45 sequence as described.
Kit comprising immunogenic composition and codon harmonized components
A kit including an immunogenic composition with one or more Plasmodium falciparum or Plasmodium vivax pre-fertilization or post-fertilization antigens, instructions for reducing transmission, and one or more of the isolated codon harmonized sequence SEQ ID NO: 2 and/or the corresponding expression vector.
These inventive features collectively cover the preparation of codon harmonized antigen sequences, their incorporation into vectors and host cells for expression, and the use of these components in immunogenic compositions and kits to reduce malaria transmission.
Stated Advantages
Expression of full-length Pfs48/45 antigen in proper conformation with high yield in E. coli, overcoming previous challenges due to codon usage differences.
The recombinant antigen elicits potent transmission-blocking antibodies in both mice and non-human primates, demonstrating functional immunogenicity.
Codon harmonization allows production of correctly folded proteins which can induce long-lasting immunity and block malaria transmission effectively.
Immunogenic compositions using codon harmonized antigens provide a novel and improved approach for developing malaria transmission-blocking vaccines.
Documented Applications
Use of immunogenic compositions comprising one or more Plasmodium falciparum or Plasmodium vivax pre-fertilization or post-fertilization antigens to block transmission of malaria in a subject.
Methods of immunizing subjects against Plasmodium falciparum or Plasmodium vivax to prevent malaria infection.
Treatment or prevention of malaria in subjects through administration of immunogenic compositions comprising codon harmonized antigens.
Development of vaccines targeting sexual stages of Plasmodium to reduce parasite transmission by mosquitoes.
Use of codon harmonized gene sequences encoding Plasmodium antigens for heterologous expression in host cells (e.g., E. coli) for vaccine production.
Preparation of kits comprising immunogenic compositions and instructions for use in reducing malaria transmission or preventing malaria.
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