Genetic Vaccines

Abstract

In a few short years, genetic vaccine technology has moved rapidly from a novel concept to an important strategy for the development of human and veterinary vaccines, for numerous indications. This article discusses current areas in which further refinements in technology will influence a variety of infectious disease treatments, including intramuscular and intradermal inoculation, gene gun inoculation, the mechanism of antigen presentation, and the use of genetic adjuvants.

Plasmid Vectors Encoding Cholera Toxin or the Heat-Labile Enterotoxin fromEscherichia coliAre Strong Adjuvants for DNA Vaccines

“…CpG motifs exert their immunostimulatory potential by a pathway involving receptor-mediated endocytosis of CpG-containing DNA into immune cells (macrophages, DC, and B cells) followed by endosome acidification and likely degradation of the DNA into CpG-containing oligonucleotides (1). Particle-mediated ("gene gun") DNA vaccines bypass this signaling mechanism because of the direct intranuclear and intracytoplasmic deposition of intact plasmid DNA (23). This is evidenced by the fact that particle-mediated and needleinoculated DNA vaccines induce qualitatively different responses that are dependent on the method rather than the location of vaccine administration (17,35).…”

“…In addition to improved delivery, any DNA vaccine, with or without a specific delivery system, can potentially benefit from the inclusion of an adjuvant to augment the strength or quality of a given response. To this end, several investigators have demonstrated the ability to modulate the responses to both naked DNA and particle-based DNA vaccines by inclusion of vectors encoding a variety of cytokines and chemokines (23,24,36,40,46).Our efforts to identify a safe and potent adjuvant for particle-mediated DNA vaccines have recently focused on cholera toxin (CT) and the related Escherichia coli heat-labile enterotoxin (LT). CT and LT are two of the most powerful adjuvants known, due to their ability to elicit robust mucosal and systemic responses via the mucosal and parenteral routes (37, 50).…”

“…DNA vaccines are widely recognized for their ability to elicit cellular as well as humoral immune responses to microbial antigens (23). An important characteristic of DNA vaccines is that they can mimic characteristics of live vaccines due to their ability to induce the de novo production of microbial antigens in both transiently transfected nonimmune cells and antigenpresenting cells in the vaccine inoculation site and nearby draining lymph nodes (12,14,25).…”

“…In addition to improved delivery, any DNA vaccine, with or without a specific delivery system, can potentially benefit from the inclusion of an adjuvant to augment the strength or quality of a given response. To this end, several investigators have demonstrated the ability to modulate the responses to both naked DNA and particle-based DNA vaccines by inclusion of vectors encoding a variety of cytokines and chemokines (23,24,36,40,46).…”

Immunogenicity Evaluation of DNA Vaccines That Target Guinea Pig Cytomegalovirus Proteins Glycoprotein B and UL83

“…There has also been considerable recent interest in development of novel, nucleic acid-based DNA vaccines for prevention of herpesvirus infections (29). These vaccines are simple to produce and administer, and induce both humoral and cell-mediated immune responses (19). HCMV gB and UL83 DNA vaccines induce antibody responses in mice (12,21,24), but there is little information about CMV DNA vaccine responses in relevant, species-specific models, and there have been no previous reports of GPCMV DNA vaccines.…”