DNA Vaccines: Immunology, Application, and Optimization

Abstract

The development and widespread use of vaccines against infectious agents have been a great triumph of medical science. One reason for the success of currently available vaccines is that they are capable of inducing long-lived antibody responses, which are the principal agents of immune protection against most viruses and bacteria. Despite these successes, vaccination against intracellular organisms that require cell-mediated immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and human immunodeficiency virus infection, are either not available or not uniformly effective. Owing to the substantial morbidity and mortality associated with these diseases worldwide, an understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. For these reasons, a new form of vaccination, using DNA that contains the gene for the antigen of interest, is under intensive investigation, because it can engender both humoral and cellular immune responses. This review focuses on the mechanisms by which DNA vaccines elicit immune responses. In addition, a list of potential applications in a variety of preclinical models is provided.

Protection of Guinea Pigs against Leptospira interrogans Serovar Lai by LipL21 DNA Vaccine

“…DNA vaccination has recently been tested for many pathogens. Thus far, it has exhibited some promising results (12). It has been known that antigen-specific immune responses can be elicited by the intramuscular inoculation of a plasmid containing foreign DNA expressed (13,14).…”

CCL19 (ELC) as an adjuvant for DNA vaccination: induction of a TH1-type T-cell response and enhancement of antitumor immunity

“…There is evidence from different animal models that in vivo transfection of dendritic cells (DC) plays a crucial role in inducing immunity after injection of plasmid DNA (pDNA) coding for tumor antigens. [1][2][3] DNA vaccines combine the most desirable attributes under the aspect of clinical application against cancer: they (1) code for multiple major histocompatibility complex (MHC) class I-and class IIrestricted epitopes, which may be presented to both CD4 þ and CD8 þ T cells, (2) lead to a preferential MHC class-I expression of the antigen, (3) contain CpGrich sequences that are strongly immunogenic, (4) can be produced as a 'general' vaccine being applicable to any individual and (5) are not afflicted with safety concerns like viral vectors. [1][2][3] Despite induction of both cellular and humoral immune responses by DNA vaccines, application against cancer has been hampered in many cases by the failure of the vaccine to induce tumor rejection.…”

“…[1][2][3] DNA vaccines combine the most desirable attributes under the aspect of clinical application against cancer: they (1) code for multiple major histocompatibility complex (MHC) class I-and class IIrestricted epitopes, which may be presented to both CD4 þ and CD8 þ T cells, (2) lead to a preferential MHC class-I expression of the antigen, (3) contain CpGrich sequences that are strongly immunogenic, (4) can be produced as a 'general' vaccine being applicable to any individual and (5) are not afflicted with safety concerns like viral vectors. [1][2][3] Despite induction of both cellular and humoral immune responses by DNA vaccines, application against cancer has been hampered in many cases by the failure of the vaccine to induce tumor rejection. Therefore, in the past there have been several efforts to augment immunogenicity of DNA vaccines, most of them aiming at one of the following strategies: (1) coexpression of immunomodulatory molecules such as cytokines, co-stimulatory molecules or chemokines, 4 (2) enhancing DC-directed antigen uptake and (3) amplification of DC recruitment at the site of antigen expression, that is, by administration of Flt-3L.…”

CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC

“…This process results in efficient T-cell priming within secondary lymphatic tissues. [4][5][6][7] Although DNA vaccines have been very successful in inducing antigen-specific immune responses in mice, [8][9][10] immunogenicity in humans and large animals has so far been largely disappointing. 3,9,11 The reasons are diverse, but are mostly related to topics such as dosing, application route, tissue distribution and differences in toll-like receptor (TLR) expression patterns between mice and humans.…”