VACCINES

Vaccines are biochemical or biological formulations that stimulate a protective immune response (vaccination) which is intended to prevent disease upon subsequent contact with the pathogen by evoking B-cell (antibody response) and T-cell stimulation. Vaccines activate the immune system by mimicking a microbial invasion without the harmful, sometimes fatal, consequences of an infection while their effectiveness is assessed in terms of percentage of recipients protected and the duration and degree of protection (1).

The recombinant DNA strategy in developing new vaccines, applied in the recent history of modern medicine is performed by identifying the specific component(s) that can elicit the production of protective antibodies, and then cloning and expressing the gene encoding protein. This form of antigen produced inside the cell is presented and processed by both MHC class I and class II inducing restricted cellular and humoral immuneresponses (2, 3). This approach has made possible a safe and effective recombinant vaccine against hepatitis B virus, which has replaced the vaccine derived from the plasma of hepatitis B virus-infected individuals.

Moving into the 21st century, rational vaccine design remains an ambitious goal while understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. Although classical methods are still providing new vaccines, the impact of scientific and biotechnology progress has multiplied the strategies to improve vaccines. While animal studies have been extremely important to unravel the fundamental mechanisms that govern the immune response, vaccinologists are still facing the challenge of understanding thehuman immune system in its complexity and genetic heterogeneity and in unravelling the sophisticated escape mechanisms used by human pathogens (4, 5). 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 [6]. DNA vaccines usually consist of plasmid vectors (derived from bacteria) that contain heterologous genes (transgenes) inserted under the control of a eukaryotic promoter, allowing protein expression in mammalian cells [7]. An important consideration when optimising the efficacy of DNA vaccines is the appropriate choice of plasmid vector. The basic requirements for the backbone of a plasmid DNA vector are a eukaryotic promoter, a cloning site, a polyadenylation sequence, a selectable marker and a bacterial origin of replication [8].

DNA immunization offers many advantages over the traditional forms of vaccination. It is able to induce the expression of antigens that resemble native viral epitopes more closely than standard vaccines do since live attenuated and killed vaccines are often altered in their protein structure and antigenicity. DNA vaccines encoding several antigens or proteins can be delivered to the host in a single dose, only requiring a microgram of plasmids to induce immune responses. Rapid and large-scale production is very temperature stable making storage and transport much easier. Another important advantage of genetic vaccines is their therapeutic potential for ongoing chronic viral infections.  DNA vaccination may provide an important tool for stimulating an immune response in HBV, HCV and HIV patients. The continuous expression of the viral antigen caused by gene vaccination in an environment containing many APCs may promote successful therapeutic immune response which cannot be obtained by other traditional vaccines [6].

References:

  1. Karen L. Goldenthal, Karen Midthun, and Kathryn C. Zoon. Medical Microbiology, 4th ed. Baron S. Control of Viral Infections and Diseases, Chapter 51.
  2. De-chu C Tang and Kent R Van Kampen. Toward the development of vectored vaccines in compliance with evolutionary medicine. Expert Review of Vaccines, 2008; 7(4):399-402.
  3. Encke, J., Jasper zu Putlitz, and Jack R. Wands. DNA Vaccines. Intervirology 1999; 42:117-124.
  4. Ertl HC, Lanzavecchia A. Current Opinion inImmunology. Vaccines. Introduction. CurrOpin Immunol. 2010; 22(3):355-7.
  5. Koprowski, H, and D.B. Weiner. 1998. DNA Vaccination/ Genetic Vaccination. Spriner-Verlag, Heidelberg, 198p.
  6. Davis HL: Plasmid DNA expression systems for the purpose of immunisation. Curr. Opin. Biotechnol 1997; 8:635-640.
  7. Gurunathan S, Klinman DM and Seder RA: DNA vaccines: immunology, application, and optimization. Ann. Rev. Immunol. 2000; 18:927-974.
  8. Chapman BS, Thayer RM, Vincent KA and Haigwood NL: Effect of intron A from human cytomegalovirus (Towne) immediate early gene on heterologous expression in mammalian cells. Nucleic Acids Res 1991; 9:3979-3986.
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