title: Evaluation of the Impact of Codon Optimization and N-Linked Glycosylation on Functional Immunogenicity of Pfs25 DNA Vaccines Delivered by In Vivo Electroporation in Preclinical Studies in Mice.
abstract: Plasmodium falciparum sexual stage surface antigen Pfs25 is a well-established candidate for malaria transmission-blocking vaccine development. Immunization with DNA vaccines encoding Pfs25 has been shown to elicit potent antibody responses in mice and nonhuman primates. Studies aimed at further optimization have revealed improved immunogenicity through the application of in vivo electroporation and by using a heterologous prime-boost approach. The goal of the studies reported here was to systematically evaluate the impact of codon optimization, in vivo electroporation, and N-linked glycosylation on the immunogenicity of Pfs25 encoded by DNA vaccines. The results from this study demonstrate that while codon optimization and in vivo electroporation greatly improved functional immunogenicity of Pfs25 DNA vaccines, the presence or absence of N-linked glycosylation did not significantly impact vaccine efficacy. These findings suggest that N-glycosylation of Pfs25 encoded by DNA vaccines is not detrimental to overall transmission-blocking efficacy.
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine and Vector Borne Infectious Diseases Research Center, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Dibyadyuti
authors.initials: D
authors.lastname: Datta
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine and Vector Borne Infectious Diseases Research Center, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Geetha P
authors.initials: GP
authors.lastname: Bansal
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine and Vector Borne Infectious Diseases Research Center, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Ichor Medical Systems, Inc., San Diego, California, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Ellefsen
authors.affiliation: Ichor Medical Systems, Inc., San Diego, California, USA.
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine and Vector Borne Infectious Diseases Research Center, Tulane University, New Orleans, Louisiana, USA nkumar@tulane.edu.
authors.forename: Nirbhay
authors.identifier: http://orcid.org/0000-0002-0358-4924
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D003062:Codon; D004353:Drug Evaluation, Preclinical; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006031:Glycosylation; D008288:Malaria / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D003062:Codon; D017780:Malaria Vaccines; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins; D019444:Vaccines, DNA