Abstract
DNA vaccines are stable, safe, and cost effective to produce and relatively quick and easy to manufacture. However, to date, DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172 bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits, and macaques at 4–10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.
Highlights
IntroductionDNA vaccines were hailed as long ago as the 1990s as the best thing in vaccines: Plasmid-based
DNA vaccines were hailed as long ago as the 1990s as the best thing in vaccines: Plasmid-basedDNA vaccines are relatively easy and affordable to produce, sharing a common production method for all vaccines; they are thermostable and safe with no risk of virulence or apparently of anti-vector immunity, can be administered to immunocompromised individuals, and multiple plasmids can be mixed and used as a broad spectrum combination vaccine
Despite showing promise in small animals, with some DNA vaccines being licensed for veterinary use [44,45], no DNA vaccines have been licensed for human use as immunogenicity is still relatively poor
Summary
DNA vaccines were hailed as long ago as the 1990s as the best thing in vaccines: Plasmid-based. DNA vaccines are relatively easy and affordable to produce, sharing a common production method for all vaccines; they are thermostable and safe with no risk of virulence or apparently of anti-vector immunity, can be administered to immunocompromised individuals, and multiple plasmids can be mixed and used as a broad spectrum combination vaccine. DNA vaccines elicit mainly cell-mediated immune responses due to presentation of expressed antigens via major histocompatibility complex class I (MHC-I) presentation, which is similar to viral pathogens and a desirable feature of a vaccine [1]. One important drawback to DNA vaccines, is their lack of immunogenicity compared to protein-based or whole virus vaccines: Humoral responses are generally weak if not lacking altogether, and high, repeated doses of DNA are needed in order to obtain reasonable response rates in animal models. Results in small experimental animals have not translated well into human clinical trial results, and there are concerns over the safety of injecting large amounts of DNA (milligrams) into humans [2]
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