Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation

Authors

Dibyadyuti Datta, Tulane University School of Public Health and Tropical Medicine
Geetha P. Bansal, Tulane University School of Public Health and Tropical Medicine
Dietlind L. Gerloff, Foundation for Applied Molecular Evolution
Barry Ellefsen, Ichor Medical Systems, Inc.
Drew Hannaman, Ichor Medical Systems, Inc.
Nirbhay Kumar, Tulane University School of Public Health and Tropical Medicine

Document Type

Journal Article

Publication Date

1-5-2017

Journal

Vaccine

Volume

35

Issue

2

DOI

10.1016/j.vaccine.2016.11.072

Keywords

Combination antigens; DNA vaccine; Electroporation; Glycosylation; Malaria

Abstract

© 2016 Elsevier Ltd 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.

APA Citation

Datta, D., Bansal, G., Gerloff, D., Ellefsen, B., Hannaman, D., & Kumar, N. (2017). Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation. Vaccine, 35 (2). http://dx.doi.org/10.1016/j.vaccine.2016.11.072