Preclinical and clinical progress of particle-mediated DNA vaccines for infectious diseases

Abstract

This review provides an overview of studies employing particle-mediated epidermal delivery (PMED) or the gene gun to administer DNA vaccines for infectious diseases in preclinical studies employing large animal models and in human clinical trials. It reviews the immunogenicity and protective eYcacy of PMED DNA vaccines in nonhuman primates and swine and studies that have directly compared the eVectiveness of PMED in these large animal models to existing licensed vaccines and intramuscular or intradermal delivery of DNA vaccines with a needle. Various clinical trials employing PMED have been completed and an overview of the immunogenicity, safety, and tolerability of this approach in humans is described. Finally, eVorts currently in progress for commercial development of particle-mediated DNA vaccines are discussed.

Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

“…Some strategies to overcome the limitations in immunogenicity of the platform include gene optimization, heterologous prime-boost strategies, improved delivery techniques, as well as the use of molecular adjuvants to augment DNA vaccine-elicited responses. 1,[7][8][9][10][11] The inclusion of genes encoding cytokines or chemokines (immune trafficking signals) in a vaccination strategy can alter the magnitude, duration and nature of the immune response and such genes have been tested as vaccine adjuvants. [12][13][14][15][16][17] These strategies have shown promise in improving the efficacy of DNA vaccines in large-animal models such as horses, dogs and pigs, as well as in humans.…”

Systemic DNA immunization against ovine lentivirus using particle-mediated epidermal delivery and modified vaccinia Ankara encoding the gag and/or env genes

“…Particle--mediated epidermal delivery (PMED) has been used in many vaccine studies with increasing success not only in rodent models but also in humans, non--human primates and several veterinary species [13]. Comparisons of PMED with needle--based approaches to DNA vaccine delivery show that PMED often induces higher antibody and CD8+ T cell responses [14] and [15].…”

DNA Vaccination by Electrogene Transfer

“…Moreover, antigen and adjuvant molecules can be delivered to the same cell at the same time being entrapped together in biodegradable microparticles such as poly-lactide-co-glycolide (PLG) or chitosan, or complexed with non-ionic block copolymers or polycations such as polyethyleneimine. Microparticulate adjuvants are currently tested in some clinical trials against human immunodeficiency virus (HIV), hepatitis B virus (HBV) and influenza (Fuller et al 2006). DNA entrapment or encapsulation into biodegradable microspheres for DNA vaccine delivery has been illustrated in patent WO0203961 (Johnson 2003).…”

“…Because the DNA carrier is introduced directly into the skin cells, delivery of plasmid DNA vaccines using this strategy reduces the amount of DNA needed to induce immune responses. Robust immunogenicity has been shown in many different preclinical models and in clinical trials predominantly for infectious diseases (Fuller et al 2006). In contrast to intramuscular or intradermal injection by needle, the gene gun delivery system releases plasmid DNA directly into the cells of the epidermis (Yang et al 1990).…”

“…The advantage of using low doses of plasmid DNA is particularly attractive for prophylactic vaccines against infectious diseases, where a simple and rapid delivery is the main pre-requisite. Gene gun delivery has recently been used with success in a trial against the influenza virus, inducing sero-protective levels of antibody and it has been used in trials against HBV and HIV infections (Fuller et al 2006). A further implementation of the biolistic delivery was obtained also by creating improved injection device suitable for application in human tissues.…”