Biological Sciences
DNA Vaccine
A DNA vaccine is a type of vaccine that uses genetically engineered DNA to stimulate an immune response against a specific pathogen. The DNA encoding the antigen is injected into the body, where it is taken up by cells and used to produce the antigen, triggering an immune response. This approach has the potential to be more stable and cost-effective than traditional vaccines.
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4 Key excerpts on "DNA Vaccine"
eBook - ePub- P. J. Quinn, B. K. Markey, F. C. Leonard, P. Hartigan, S. Fanning, E. S. Fitzpatrick(Authors)
- 2011(Publication Date)
- Wiley-Blackwell(Publisher)
One of the most significant developments in vaccine production in recent years involves the use of DNA, encoding microbial antigens cloned in a bacterial plasmid, for immunization. The procedure involves injection of a plasmid containing the DNA sequence for a protective antigen whose expression is controlled by a strong mammalian promoter. For an infectious agent expressing that antigen, injection of this recom-binant plasmid into the skin or muscle of animals may result in the production of the protein inducing immunity against that infectious agent. This leads to the expression in host cells of the encoded genes with the development of a significant immune response to the gene product in the recipient. Unlike viral vectors, the recombinant plasmid cannot replicate in the mammalian cells but transfected host cells express the vaccine antigen. Methods of delivery include direct intramuscular injection and the use of liposomes or coated gold particles fired by a gene gun. Although transfection rates appear low, antigen production has been detected in animals vaccinated with DNA intramuscularly for up to 6 months after injection. Because DNA vaccination induces intracellular processing of antigen, it seems to mimic a natural infection and is, therefore, an effective method of inducing T cell responses. Even small amounts of DNA can stimulate strong cell-mediated responses. Humoral responses, however, may not be as high as those obtained by injection of a purified antigen. A strategy in which priming with DNA Vaccines is followed by boosting with attenuated viral vectors such as fowlpoxvirus and modified vaccinia virus has produced exceptionally strong immune responses (Ramshaw and Ramsay, 2000 ). The success of consecutive administration of DNA Vaccines and attenuated viral vectors was attributed to the ability of the DNA Vaccines to generate T cells of high affinity which were further stimulated by boosting with non-replicating viral vectors. Although immune responses may be delayed following DNA vaccination, a persistent response may occur. In contrast to modified live viral vaccines, maternal antibody does not appear to affect the immune response in young animals. An advantage of immunizing with purified DNA is the possibility of antigen presentation in its native form as it would occur during replication of an infectious agent in the body. By this method of vaccination, it is also possible to select genes for the antigen of interest without the need for a complex bacterial or viral vector.The safety of DNA Vaccines remains unresolved. The possibility that foreign DNA could integrate into the host chromosome and induce neoplastic changes or other cellular alterations has been suggested. It has also been suggested that DNA introduced into the body by this method of vaccination might induce anti-DNA antibodies to the recipient’s own DNA.Reverse vaccinologyAvailability of genome sequences for many infectious agents offers the possibility of exploring the complete proteome, which provides the potential for rational selection of vaccine candidates. This novel approach is termed reverse vaccinology and it can be combined with functional immunology to optimize epitope prediction, leading to development of DNA Vaccines. Depending on the nature of the infectious agent, approaches used may differ.Potential candidate vaccines have been developed using reverse vaccinology for bacterial pathogens, namely Bacillus anthracis (Ariel et al ., 2002) and Leptospira (Koizumi and Watanabe, 2005 ). The completed genome of Neisseria meningitidis group B (NMB) was searched using suitable unbiased computer algorithms to identify open reading frames (ORF) encoding surface-exposed protein antigens, which could later be evaluated as potential vaccines (Fig. 5.4 ) based on their ability to elicit a bactericidal antibody response (Pizza et al ., 2000; Tan et al
eBook - ePubBiological Drug Products
Development and Strategies
- Wei Wang, Manmohan Singh(Authors)
- 2013(Publication Date)
- Wiley(Publisher)
49. Geall AJ, Verma A, Otten GR, Shaw CA, Hekele A, Banerjee K, et al. Nonviral delivery of self-amplifying RNA vaccines. Proc Natl Acad Sci USA 2012;109(36):14604–14609.50. Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol 2012;30(12):1210–1216.51. Geall AJ, Verma A, Otten GR, Shaw CA, Hekele A, Banerjee K, et al. Enhancement of cellular immune response in HIV-1 seropositive individuals: a DNA-based trial. Clin Immunol 1999;90(1):100–107.52. Boyer JD, Cohen AD, Vogt S, Schumann K, Nath B, Ahn L, et al. Vaccination of seronegative volunteers with a human immunodeficiency virus type 1 env/rev DNA Vaccine induces antigen-specific proliferation and lymphocyte production of beta-chemokinesJ Infect Dis 2000;181(2):476–83.53. Dean HJ, Chen D.Epidermal powder immunization against influenza. Vaccine 2004;23(5):681–686.54. Drape RJ, Macklin MD, Barr LJ, Jones S, Haynes JR, Dean HJ.Epidermal DNA Vaccine for influenza is immunogenic in humans. Vaccine 2006;24(21):4475–4481.55. Jones S, Evans K, McElwaine-Johnn H, Sharpe M, Oxford J, Lambkin-Williams R, et al. DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial. Vaccine 2009;27(18):2506–2512.56. Roy MJ, Wu MS, Barr LJ, Fuller JT, Tussey LG, Speller S, et al. Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA Vaccine. Vaccine 2000;19(7–8):764–778.57. Robinson HL.Prime boost vaccines power up in people. Nat Med 2003;9(6):642–643.58. Lu S.Heterologous prime-boost vaccination. Curr Opin Immunol 2009;21(3):346–351.59.
eBook - ePub- Ralph Rapley, Ralph Rapley(Authors)
- 2021(Publication Date)
- Royal Society of Chemistry(Publisher)
The main obstacle encountered with nucleic acid vaccines is the overall low efficiency of production of the desired antigens due to two main factors, cellular uptake and immunogenicity. DNA Vaccines must cross the plasma membrane and then the nuclear membrane prior to producing mRNA, which then must exit the nucleus for translation. RNA vaccines are more direct in that there is no requirement for nuclear transport; however, cellular uptake is low and RNA is subject to degradation by cellular RNases, which reduces their overall efficacy. Several strategies have been employed to address these issues and include delivery systems to increase vaccine uptake and modifications to the basic constructs to increase translation efficiency. This section considers the design issues and potential of plasmid DNA and RNA vaccines.16.6.1 DNA Vaccines
The potential use of plasmid DNA as vaccines was realised in the 1990s with the demonstration that a marker protein encoded in a simple plasmid DNA could be expressed in mammalian cells.93Subsequently, it was demonstrated that plasmids encoding viral proteins elicited protective antibody and CTL responses.95 ,96The basic principle underlying DNA Vaccines is that the antigenic proteins of interest are expressed in vivo in the cells of the immunised individual. These proteins are then processed through the cytosolic pathway within the host cells, leading to MHC class I presentation to CTLs. Secreted proteins can be taken up by DCs and processed for class II presentation to TH cells. DCs may also cross-present these proteins to both TH cells and CTLs. Although no DNA Vaccines have been approved for use in humans, four vaccines have been approved for use in veterinary medicineinclude, namely vaccines against West Nile virus (WNV) in horses,97infectious haematopoietic necrosis virus in farmed salmon,98a therapeutic vaccine for melanoma in dogs99and a vaccine encoding growth hormone-releasing hormone (GHRH) for preventing fetal loss in pigs.100Plasmid DNA offers several advantages over conventional live vaccines in that they are non-replicating, cannot be transmitted and are unlikely to change to a pathogenic state – a risk with live, attenuated vaccines. Several studies have generated a great deal of information on the safety, immunogenicity, design and formulation of plasmid DNA Vaccines.101 ,104Clinical trials have shown that these preparations are well tolerated and safe for use in humans,105although there are lingering concerns about the potential risks of genomic integration, as with viral vectors. A number of plasmid DNA Vaccines are under development and have been clinically tested in humans and other species against both infectious pathogens and cancers.106 ,110As mentioned above, owing to the speed of production, many of the recent trials have been focused on their use in disease outbreak situations.94In the recent Zika virus disease outbreak in Brazil, DNA Vaccines were in clinical trials within months of the outbreak.111
eBook - ePub- Peter J. Delves, Seamus J. Martin, Dennis R. Burton, Ivan M. Roitt(Authors)
- 2016(Publication Date)
- Wiley-Blackwell(Publisher)
Plasmodium berghei produced high levels of peptide‐specific CD8 T‐cells secreting IFNγ, which protected against challenge by sporozoites.Induction of memory cells by DNA Vaccine and boost of antibody production with the protein immunogen, human chorionic gonadotropin β‐chain (hCG β). Groups of five (C57BL/6 × BALB/c)F1 mice each received 50 mg of the hCG β DNA plasmid at weeks 0 and 2; one group received a further injection of the plasmid, while the other was boosted with 5 mg of the hCG β protein antigen in Ribi adjuvant. Dilutions of serum were tested for antibodies to hCG β by indirect ELISA. Mean titers + SE are shown.Figure 12.11(Data source: Laylor R. et al. (1999) Clinical and Experimental Immunology 117, 106.)Recently, considerable excitement has focused on RNA vaccines, which have several major advantages over DNA. First, RNA needs only to be delivered into the cytoplasm of the host cell to be translated into protein, whereas DNA must first be transcribed into mRNA in the nucleus, before back into the cytoplasm for translation. Second, the safety concerns associated with potential integration of DNA into host chromosomes is absent for RNA. Third, RNA can have a very strong adjuvant effect by triggering innate responses that can lead eventually to more effective adaptive immune responses. The major disadvantage that has classically been associated with RNA is its very low stability compared to DNA. However, recent advances in formulation and delivery have largely overcome these disadvantages. There are two principal forms of RNA vaccine: (i) conventional, non‐amplifying mRNA and (ii) RNA replicons engineered from the genomes of positive‐strand RNA viruses, especially alphaviruses such as Sindbis, Semliki Forest, and Venezuelan equine encephalitis (VEE) viruses. The conventional approach requires high doses of mRNA to achieve good levels of antigen although optimization protocols have helped. The great strength of the second approach is that amplification of RNA (self‐amplifying mRNA [SAM]) occurs within host cells to generate large amounts of antigen. Proof of concept of RNA vaccines has now been demonstrated in a number of animal models and many predict this will be a key vaccine platform for the future.
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