Genetic Vaccines and Therapy

The complexity of parasitic infections requires novel approaches to vaccine design. The versatility of DNA vaccination provides new perspectives. This review discusses the use of prime-boost immunizations, genetic adjuvants, multivalent vaccines and codon optimization for optimal DNA vaccine design against parasites. Introduction DNA vaccination was introduced in 1990 by a study that demonstrated the induction of protein expression upon direct intramuscular injection of plasmid DNA in myocytes [1]. DNA vaccines are new types of sub-unit vaccines allowing protein expression in mammalian cells after introduction of plasmid or recombinant viral vectors encoding the selected protective antigen. Protective immunity conferred by DNA vaccines has been shown in many animal models of various diseases including HIV, tuberculosis and cancer [2-4]. DNA vaccines induce strong humoral and cellular immunity and have the potential to increase immunogenicity through modifications of the vector or incorporation of adjuvant-like cytokine genes. Successful vaccines should be able to induce strong immune responses which are long-lasting and in most cases providing protection against different strains of the same pathogen. Progress has been made towards development of DNA vaccines against viral and bacterial pathogens showing protection and lasting immunity [5]. Application of this new vaccination technology with regard to parasitic infection provides new hope for significant advances in anti-parasitic vaccine research. An important consideration in developing vaccines against parasites is the complexity of parasitic diseases. Parasite infections, unlike most viral and bacterial infections, tend to be chronic and associated with immunodepression or inappropriate immune responses [6]. Parasites have complex life cycles and host immunity to stage-specific antigens may not overlap with other later stages or vectorborne stages. Antigenic variation and other immune evasion mechanisms also complicate the development of vaccines against parasites. However, with recombinant DNA technology and the versatility of DNA vaccination, it is now possible to take rational parasite specific strategies to vaccine design and overcome the obstacles presented by parasitic diseases. Improving DNA vaccine efficacy against parasitic disease can be achieved by: prime-boost immunizations, genetic adjuvants, multivalent vaccines or codon optimization. This review describes the application of these strategies, using specific parasites as examples, to improve DNA vaccine efficacy (see Table 1[7-19]). Prime-Boost Immunizations Current sub-unit vaccines predominantly induce strong antibody responses and weak cellular immunity. DNA vaccines in animal models can induce both strong humoral and cellular mediated responses, but although safe in humans, DNA vaccines do not produce the same Published: 03 December 2004 Genetic Vaccines and Therapy 2004, 2:17 doi:10.1186/1479-0556-2-17 Received: 05 October 2004 Accepted: 03 December 2004 This article is available from: http://www.gvt-journal.com/content/2/1/17 © 2004 Ivory and Chadee; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.