title: Protective immune responses to biolistic DNA vaccination of Brugia malayi abundant larval transcript-2.
abstract: Biolistic vaccination using gene gun is developed as a safer tool for delivery of DNA vaccines, a technique that combines high vaccine efficiency with lower antigen dosage and lower cost per vaccine dose. In this study, we compared the protective responses in mice after delivering the Brugia malayi abundant larval transcript-2 (BmALT-2) DNA vaccine using the conventional intradermal approach or with the needleless gene gun delivery approach. BmALT-2 is a leading vaccine candidate against B. malayi, a lymphatic filarial parasite of human. After optimizing the DNA dose and gene gun parameters for delivery into mouse skin, groups of mice were biolistically vaccinated with 5 μg of BmALT-2pVAX. Groups of mice vaccinated intradermally with 5 μg or 100 μg of BmALT-2pVAX was used for comparison of vaccine efficacy. Results demonstrated that gene gun vaccination with 5 μg of BmALT-2pVAX conferred significant protection against challenge infection that was comparable to the degree of protection conferred by intradermal vaccination with 100 μg of BmALT-2pVAX. This observation was further supported by an in vitro antibody dependent cellular cytotoxicity (ADCC) assay. Analysis of the immune response showed that the gene gun vaccination predominantly induced an IgG1 antibody response and significantly high Th2 cytokine response (IL-4) from spleen cells compared to intradermal BmALT-2 DNA delivery that induced predominantly an IgG2a and Th1 cytokine response (IFN-γ, IL-12 and TNF-α). These findings show that host protective responses could be achieved with 20 fold decrease in DNA dose using a gene gun and could prove to be an efficient delivery method in BmALT-2 DNA vaccination against lymphatic filariasis.
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Joseph
authors.forename: S
authors.initials: S
authors.lastname: Sambanthamoorthy
authors.forename: G
authors.initials: G
authors.lastname: Dakshinamoorthy
authors.forename: G
authors.initials: G
authors.lastname: Munirathinam
authors.forename: K
authors.initials: K
authors.lastname: Ramaswamy
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology*; D019470:Biolistics / Q000379:methods*; D019556:COS Cells; D002522:Chlorocebus aethiops; D018509:DNA, Helminth / Q000276:immunology; D004605:Elephantiasis, Filarial / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014612:Vaccines / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: C521555:ALT-2 protein, Brugia malayi; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D018509:DNA, Helminth; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma