Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation
| Autor: | Dietlind L. Gerloff, Dibyadyuti Datta, Geetha P. Bansal, Drew Hannaman, Nirbhay Kumar, Barry Ellefsen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Protozoan Proteins Antibodies Protozoan Antigens Protozoan Article DNA vaccination law.invention 03 medical and health sciences chemistry.chemical_compound Plasmid Antigen law Malaria Vaccines Disease Transmission Infectious Vaccines DNA Animals Malaria Falciparum Mice Inbred BALB C Membrane Glycoproteins General Veterinary General Immunology and Microbiology biology Electroporation Immunogenicity Public Health Environmental and Occupational Health Plasmodium falciparum biology.organism_classification Virology Molecular biology 030104 developmental biology Infectious Diseases chemistry Recombinant DNA Molecular Medicine Female DNA |
| Zdroj: | Vaccine. 35(2) |
| ISSN: | 1873-2518 |
| Popis: | Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses. DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP). EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine. Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated). Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines. Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes. |
| Databáze: | OpenAIRE |
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