Rational Design of Formulated DNA Vaccines: The DermaVir Approach
DermaVir features three key technological elements of a rational vaccine design: a single plasmid DNA immunogen to express 15 HIV antigens, a synthetic pDNA nanomedicine formulation and a topical dendritic cell-targeting vaccine administration. Its novel
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Rational Design of Formulated DNA Vaccines: The DermaVir Approach Eszter Nátz and Julianna Lisziewicz
DermaVir features three key technological elements of a rational vaccine design: a single plasmid DNA immunogen to express 15 HIV antigens, a synthetic pDNA nanomedicine formulation and a topical dendritic cell-targeting vaccine administration. Its novel mechanism of action has been consistently demonstrated in mice, rabbits, primates and human subjects: DermaVir nanomedicine is naturally transported by epidermal Langerhans cells to the lymph nodes to express the plasmid DNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity. Safety, immunogenicity and preliminary efficacy of DermaVir have been clinically demonstrated in HIV-infected human subjects. DC-based therapeutic vaccination might offer a new treatment paradigm for cancer and infectious diseases.
Background and Rationale for the Development of DermaVir Therapeutic Vaccine Against HIV/AIDS In the eighteenth century Edward Jenner developed the first prophylactic vaccine for protection against smallpox (Variola major). He used skin scarification to deliver a live whole pathogen, the cowpox vaccinia virus (VACV). While he didn’t know it at the time, Jenner’s technology induced durable and fully protective antibodies and cytotoxic T cell responses leading to the prevention and later to the eradication of smallpox infection. It has been recently demonstrated that not only the cross-protective antigen and the live virus formulation but also the vaccine administration via skin scari fication was essential for the exceptional efficacy of VACV vaccine (Liu et al. 2010).
J. Lisziewicz (*) Genetic Immunity, Berlini u. 47-49, 1045, Budapest, Hungary e-mail:[email protected] J. Thalhamer et al. (eds.), Gene Vaccines, DOI 10.1007/978-3-7091-0439-2_6, © Springer-Verlag/Wien, 2012
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E. Nátz and J. Lisziewicz
A decade later in 1885 Louis Pasteur developed the first therapeutic vaccine against rabies virus. The cross-reactive antigen and the live virus formulation mirrored Jenner’s vaccine but, instead of using a related virus, this vaccine contained a live attenuated version of the rabies virus. Pasteur then went on to replace the single vaccine administration via skin scarification with multiple injections. Since Pasteur, needle injections are widely used for the administration of vaccines. For the past 200 years vaccine development was based on empirical science. Recent vaccine products contain antigens, generally a single protein of the target pathogen capable of eliciting humoral immune responses (Donnelly et al. 1997; Ada 2005). Compared to live-attenuated vaccines these protein-based vaccinations are much safer, decreasing the risk of potential infection; however, they are less effective immunogens in inducing antibodies and cytotoxic T cell responses even when formulated with adjuvants. Recently, rational vaccine design has replaced the empirical approaches with three key elements (Douek et al. 2006; Rap
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