Vaccines: DNA

Abstract

Immunization by injection of plasmids encoding foreign proteins has successfully been used as a research tool and to elicit protective immune responses in animal models. Successful licensure of three deoxyribonucleic acid (DNA) vaccines for animal health applications has recently been attained, including two for prevention of viral diseases and one for treatment of cancer in dogs. However, DNA vaccines have so far not been sufficiently potent in humans to support licensure. Hence, much effort has been undertaken to increase the potency of DNA vaccines.

Keywords: bacteria; cancer; immunity; plasmid; vaccine; virus

Figure 1.

Mechanism of action of DNA vaccines. After administration, cellular uptake of DNA vaccines possibly occurs by a phagocytic process (step 1). Within the phagosome, some plasmid DNA molecules are partially digested to release immunostimulatory oligonucleotides that stimulate the innate immune system via TLR9 (step 2). Other plasmid DNA molecules enter the cytoplasm and are internalized by the nucleus, resulting in transcription and production of antigen encoded by the DNA vaccine. When expressed by APCs, the antigens can then be processed and presented by MHC class I or II molecules directly to naïve T cells (step 3). Alternatively, the antigens released from DNA‐transfected cells (e.g. by secretion or apoptosis) can interact with B cells to prime antigen‐specific antibodies (step 4) or be internalized by bystander APCs such as DC for indirect presentation by MHC molecules (step 5). This concomitant production of antigen and innate immune activation can promote memory immune responses to provide protection against subsequent exposure to the pathogen from which the antigen was derived.

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Further Reading

Daudel D, Weidinger G and Spreng S (2007) Use of attenuated bacteria as delivery vectors for DNA vaccines. Expert Review of Vaccines 6(1): 97–110.

Dean HJ (2005) Epidermal delivery of protein and DNA vaccines. Expert Opinion on Drug Delivery 2(2): 227–236.

Donnelly JJ, Ulmer JB, Shiver JW and Liu MA (1997) DNA vaccines. Annual Review of Immunology 15: 617–648.

Gurunathan S, Klinman DM and Seder RA (2000) DNA vaccines: Immunology, application, and optimization. Annual Review of Immunology 18: 927–974.

Laddy DJ and Weiner DB (2005) From plasmids to protection: a review of DNA vaccines against infectious diseases. International Reviews of Immunology 25(3–4): 99–123.

Liu MA and Ulmer JB (2005) Human clinical trials of plasmid DNA vaccines. Advances in Genetics 55: 25–40.

Nichols WW, Ledwith BJ, Manam SV and Troilo PJ (1995) Potential DNA vaccine integration into host cell genome. Annals of the New York Academy of Sciences 772: 30–39.

Robertson JS and Griffiths E (2006) Assuring the quality, safety, and efficacy of DNA vaccines. Methods in Molecular Medicine 127: 363–374.

Shaw DR and Strong TV (2006) DNA vaccines for cancer. Frontiers in Bioscience 11: 1189–1198.

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Ulmer, Jeffrey B, and Donnelly, John J(Dec 2007) Vaccines: DNA. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000492.pub2]