Abstract
DNA vaccines against infection with Plasmodium have been highly successful in rodent models of malaria and have shown promise in the very limited number of clinical trials conducted so far. The vaccine platform is highly attractive for numerous reasons, such as low cost and a very favorable safety profile. Gene gun delivery of DNA plasmids drastically reduces the vaccine dose and does not only have the potential to make vaccines more accessible and affordable, but also simplifies (a) the testing of novel antigens as vaccine candidates, (b) the testing of antigen combinations, and (c) the co-delivery of antigens with molecular adjuvants such as cytokines or costimulatory molecules. Described in this chapter are the preparation of the inoculum (i.e., DNA plasmids attached to gold particles, coating to the inside of plastic tubing also referred to as gene gun “bullets” or cartridges), the gene gun vaccination procedure, and the challenge of mice with Plasmodium berghei parasites to test the efficacy of the experimental vaccine.
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References
Donnelly JJ et al (1997) DNA vaccines. Annu Rev Immunol 15:617–648
Kopycinski J et al (2012) A DNA-based candidate HIV vaccine delivered via in vivo electroporation induces CD4 responses toward the alpha4beta7-binding V2 loop of HIV gp120 in healthy volunteers. Clin Vaccine Immunol 19(9):1557–1559
Ferraro B et al (2011) Clinical applications of DNA vaccines: current progress. Clin Infect Dis 53(3):296–302
Ledgerwood JE et al (2012) Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans. Clin Vaccine Immunol 19(11):1792–1797
Vardas E et al (2012) Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU((R))-Multi-HIVB, in untreated HIV-1 infected subjects. Vaccine 30(27):4046–4054
Koup RA et al (2010) Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses. PLoS One 5(2), e9015
Diaz CM et al (2013) Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors. J Transl Med 11:62
Leitner WW et al (1997) Immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from Plasmodium berghei malaria parasites. J Immunol 159(12):6112–6119
Sedegah M et al (1994) Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc Natl Acad Sci U S A 91(21):9866–9870
Kumar R et al (2013) Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons. Vaccine 31(31):3140–3147
Ferraro B et al (2013) Inducing humoral and cellular responses to multiple sporozoite and liver-stage malaria antigens using exogenous plasmid DNA. Infect Immun 81(10):3709–3720
Walsh DS et al (2006) Heterologous prime-boost immunization in rhesus macaques by two, optimally spaced particle-mediated epidermal deliveries of Plasmodium falciparum circumsporozoite protein-encoding DNA, followed by intramuscular RTS,S/AS02A. Vaccine 24(19):4167–4178
Richie TL et al (2012) Clinical trial in healthy malaria-naive adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA. Hum Vaccin Immunother 8(11):1564–1584
Chuang I et al (2013) DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity. PLoS One 8(2), e55571
Bergmann-Leitner ES, Leitner WW (2013) Improving DNA vaccines against malaria: could immunization by gene gun be the answer? Ther Deliv 4(7):767–770
Ledgerwood JE et al (2013) Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis 208(3):418–422
Bergmann-Leitner ES, Leitner WW (2013) Gene gun immunization to combat malaria. Methods Mol Biol 940:269–284
Leitner WW et al (2009) Enhancement of DNA tumor vaccine efficacy by gene gun-mediated codelivery of threshold amounts of plasmid-encoded helper antigen. Blood 113(1):37–45
Loudon PT et al (2010) GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates. PLoS One 5(6), e11021
Leitner WW et al (2003) Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways. Nat Med 9(1):33–39
Ozaki LS, Gwadz RW, Godson GN (1984) Simple centrifugation method for rapid separation of sporozoites from mosquitoes. J Parasitol 70(5):831–833
Mairhofer J, Lara AR (2014) Advances in host and vector development for the production of plasmid DNA vaccines. Methods Mol Biol 1139:505–541
Leitner WW et al (2000) Enhancement of tumor-specific immune response with plasmid DNA replicon vectors. Cancer Res 60(1):51–55
Bergmann-Leitner ES et al (2005) C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria. Int Immunol 17(3):245–255
Bergmann-Leitner ES et al (2011) Cellular and humoral immune effector mechanisms required for sterile protection against sporozoite challenge induced with the novel malaria vaccine candidate CelTOS. Vaccine 29(35):5940–5949
Scheiblhofer S et al (2001) Removal of the circumsporozoite protein (CSP) glycosylphosphatidylinositol signal sequence from a CSP DNA vaccine enhances induction of CSP-specific Th2 type immune responses and improves protection against malaria infection. Eur J Immunol 31(3):692–698
Bergmann-Leitner ES et al (2009) Molecular adjuvants for malaria DNA vaccines based on the modulation of host-cell apoptosis. Vaccine 27(41):5700–5708
Leitner WW, Restifo NP (2003) DNA vaccines and apoptosis: to kill or not to kill? J Clin Invest 112(1):22–24
Smith TG et al (2002) Innate immunity to malaria caused by Plasmodium falciparum. Clin Invest Med 25(6):262–272
Bergmann-Leitner ES et al (2007) C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei. Vaccine 25(45):7732–7736
Leitner WW, Bergmann-Leitner ES, Angov E (2010) Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy. Malar J 9:145
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Bergmann-Leitner, E.S., Leitner, W.W. (2015). Vaccination Using Gene-Gun Technology. In: Vaughan, A. (eds) Malaria Vaccines. Methods in Molecular Biology, vol 1325. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2815-6_22
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DOI: https://doi.org/10.1007/978-1-4939-2815-6_22
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