DNA vaccine: Attention turns to tatooists

by Rachel on June 15, 2010

A recent study reported the use of tattoos to stimulate the immune response to DNA vaccines. Pokorná and AL1 reveals this startling discovery in their recent article in the online journal Genetic Vaccines Open Access and therapy published. Finally, Tattoo, the simple mode can be used, is now a synonym of Medicine and tattoo artists are now taking the stage of science. The emergence of deoxyribonucleic acid (DNA) vaccines in the last ten years, seemed a promising approach for inducing immune responses are of higher quality and more durable compared to traditional vaccines, e. g. subunit, live attenuated vaccines ETC2. A DNA vaccine containing a nucleotide sequence a key role in antigenic determinant of a particular pathogen, which is then injected into a host, then transcribed and translated by host cells in a protein that is degraded into peptides that are unrelated to host3. The essence of this protein is that the immune responses induced in the host against a particular pathogen, and thus confers immunity to the host. DNA vaccine technology has great potential to improve existing immunization strategies. In 1990, Jon Wolff and colleagues found four who have been able to intramuscular injection of naked DNA in mice to be absorbed by the cell and expressed in small quantities. As has been shown to stimulate the simple injection of plasmid DNA vectors or naked DNA, could both cellular (cell mediated) and humoral (antibody) responses, have several studies on how to optimize effectiveness of vaccines are DNA. It is assumed that the slow development of immune responses after DNA vaccination is due to the fact that a small number of cells take up the injected foreign DNA. In a recent study conducted by Pokorná et al. 1, they showed that vaccination with the tattoo could be stronger humoral and cellular immune responses than intramuscular delivery supported by molecular adjuvants inducing show. This discovery has opened the door to a better understanding of how to increase the effectiveness of DNA vaccines for preventive and therapeutic vaccination improved. This discovery showed that the tattoos, not only for fashion, but an important phenomenon in medicine and this can lead to “divert attention from the tattoo artist”

Tattooing is an invasive procedure with a solid vibrating needle, the injections repeated skin wound caused both the epidermis and upper dermis in the process and results of cutaneous (skin) infections healing5.

Updating devices tattoo were used in medical research for the supply of various materials in the skin such as the study of papilloma virus in mice and rabbits from moving pigment process with cosmetic tattooing and DNA associated with the future of gene therapy of skin disease. Although DNA can be delivered by the tattoo seems to produce better humoral and cellular immune response than other methods of vaccine DNA Pokorná and compared with others, to show that by comparing the immune response produced by a tattoo or a better immune response than DNA vaccines generated more adjuvants delivered intramuscularly. They compared the DNA vaccination with different types of administration (intramuscularly compared intradermal tattoo) and two types of molecular adjuvants (pretreatment cardiovascular toxin granulocyte-macrophage colony-versus-stimulating factor (GM-CSF) of DNA co-delivery) with a mouse model. L1 major capsid protein gene of human papillomavirus type 16 (HPV16) has been used as a model antigen. This has been demonstrated that highly immunogenic in previous experiments with intramuscular administration of DNA in association with cardiovascular toxin pretreatment. PUF3L1h and PBSC / GM-CSF plasmids were used for the induction of specific immune response of antigen and adjuvant, respectively.

To assess the immune response to vaccination with the DNA of different protocols, mice immunized with the authors of the DNA anesthetized on four occasions. Each 50 micrgrams pUF3L1h plasmid (six groups) or PBSC / GM-CSF (control group) received plasmid as a single dose immunization (days 0, 14, 28 and 98). Two other groups of mice received a mixture of 50 micrograms and 50 micrograms PBSC pUF3L1h DNA / DNA each GM-CSF in a single dose. DNA was tattooed in a 10 microliter TE (Tween 80 and ether provided) for the administration of buffer alone or a plasmid of 20 microliter TE buffer to the mixture of plasmids in one or two drops on the shaved skin, was followed by a tattoo needle with a 7-linear with a tattoo machine business. Although the procedure was well tolerated, noted swelling and redness of the skin. In addition, some mice were 50 micro-liter five days cardio toxin pre-treated before the first DNA vaccination.

Blood of immunized mice was done 10 days after the third and nine days after the fourth DNA vaccination. A measure of the antigen ELISA (enzyme immunoassay) test for detection and titration test used antibody tests HPV16 L1-specific ELISPOT and L1-specific cellular immune response.

The researchers found that the effectiveness of DNA vaccine was delivered intramuscularly significantly with cardiovascular toxin pretreatment or GM-CSF DNA co-delivery has increased, but almost no effect on the intradermal tattoo vaccination. Adjuvants have a better effect after three instead of four vaccinations. But three immunizations with the method of tattoos without adjuvant significantly higher L1-specific humoral immune responses than three or four intramuscular injections of DNA by molecular adjuvants in charge. Tattooing has also triggered significantly higher L1-specific cellular immune responses of DNA combined with adjuvants and delivered intramuscularly.

Other methods used as in vivo electroporation (mechanical method of introducing polar molecules in a host cell through the cell membrane) and the delivery of the gene gun is used to deliver DNA vaccines into host cells. However, the intramuscular administration of DNA vaccines by simple injection as one of the few effective means of DNA vaccination6, 7. Although the DNA vaccine intramuscularly has the potential to result in the initiation and priming of classical Cross both at the level of proteins and nucleic acids, efforts are made to improve the absorption and expression plasmid into the professional antigen-presenting cells8 aligned. What has tattoos in honor of science is recent evidence on its usefulness in creating better immune responses to DNA vaccination. Several groups have worked only a better immune response to DNA vaccination9, 10 trigger. They combined their knowledge of immunology and DNA technology to explain what happened in the delivery of DNA into host cells. They found that when the DNA vaccine in cell introduced by intramuscular injection, the genes are transcribed and this will be the production of proteins in the cytoplasm. The secreted proteins induce cytokines, T helper cells and antibodies, to react and eliminate the pathogen. These cytokines or DNA itself cascade activated in the immune system natural killer cells that kill virus-infected cells8. It is conceivable that the robust watermark generated local tissue damage, which attracts leukocytes and this leads to local release of cytokines.

Second mechanism of action of DNA vaccines in a muscle cell (not in a position to the image of the load).

The plasmid DNA in the nucleus of the cell in place. It is transcribed and translated to make proteins in the cytoplasm of pathogens. Some of these proteins outside the cell, where he will be bound by the antibody molecules on B cells or phagocytosed by macrophages. Nevertheless, the protein is inside these cells and digested into small peptides in the groove of a cell surface protein called binding form of complex class II major histocompatibility (MHC II), similar a hot dog in a bun. T-cell receptor (TCR) on the surface of T-helper cells can recognize these peptides as foreign to the body and therefore an invading pathogen. Once peptides are bound and recognized as foreign by the TCR, T helper cells triggers a series of interleukin (IL)-proteins in both arms of the immune system (humoral and cellular stimulant) to take action. (Brookscole)

The next task for Pokorná and his colleagues, the mechanism of DNA tatto0ing determine in a mouse model induced an excellent immune response to intramuscular injection. They could not imagine that this may be due to: (a) better image of DNA by non-antigen-presenting cells (b) increased uptake of DNA by antigen presenting cells (c ) the duration of [deleted] d) induced by trauma (pain) accompany the tattoo (which is sufficient to initiate inflammatory immune system). The largest area for transfection of DNA into cells in the use of tattoos method can also be substituted for the role of GM-CSF and cardiovascular toxin (adjuvant), which is to win antigen-presenting cells, demand on the site, if you receive an intramuscular method of administration. According to these facts into consideration, it may be appropriate to say that the larger the area of DNA vaccines, covers best immune response (humoral and cell-induced).

Although this study is a revelation, offering surprising revelation that the meaning of tattoos, scientific, social and ethical implications of this study are too important to be neglected. Despite the fact that the watermarking method of the cost of delivery of DNA and the application method is standardized, the main disadvantages are (1) local trauma (pain) induced and (2) The process is somewhat cumbersome . They have also been identified by researchers. The implication is that this wonderful method, which assumes that the solution required to induce transient approach to improve immune responses to DNA vaccination may ultimately not useful for prophylactic vaccination in humans. Although it may be useful for routine immunization of animals such as cattle and human therapy, “said the researcher. The pain that can accompany this method of delivery of DNA is an issue that must be considered critical. Researchers have suggested a role for the delivery Tattoo induced by therapeutic vaccination for people because of the immune response faster and stronger. However, the benefit-risk should be taken into account before they are widely accepted as a method of delivery of DNA vaccines. Scientists with little or no option, as it exists today, which are left to embrace tattooing as a way to get the most DNA vaccines. including the many advantages of DNA vaccines: (1) quickly and in large-scale manufacture of vaccines is much cheaper than conventional vaccines (2) These vaccines are temperature stable, unlike many traditional vaccines require storage cold and have limited life. This study is to find a solution to overcome the technical scientists a way to efficiently deliver DNA into human cells and to ensure the gene is expressed when it is facing inside the cell, etc. provided

I wonder if the tattoo machine whosoever DNA vaccine delivered infections such as colds. However, for HIV / AIDS, people dare to stand in line to get the tattoo, because its benefits outweigh its pains. A very important question still begging to be asked is: how ethical is the provision of DNA vaccines by tattooing?

This study presents a strategy to generate strong humoral and cellular immune responses in mice by using DNA vaccines. Further work is needed to ensure the validity of this simple strategy and inexpensive to produce in humans.

References

First Pokorná D. et al (2008). Genetic Vaccines and Therapy 6:04 (doi: 10 1186/1479-0556-6-4)

2. Bin A. D. et al. (2005) Nature med. 11:899-904

McDonnell and Askari 3rd (1999), Medscape General Medicine at http://www. Medscape. com/viewarticle/408733

4th Wolff JA et al. (1990) Science 247:1465-1468

N. 5th Gopee V. et al. (2005) Toxicol. Appl. Pharmacol. 209: 145-158

6. Reuter J. D. et al (2001) J. Virol. Methods 98: 127-134

W. 7th T. Corder et al. (1996) Ann Allergy Asthma Immunol. 77: 222-226

8th J. Donnelly, J. et al. (2005) J. Immunol. 175: 633-639

9th HL Davis and MJ McCluskie (1999) Microbes and Infection 1: 7-21

10th J. Rice et al. (2008) Nature Reviews 8:108-120

I graduated MSc from the Institute of Molecular and Cell Biology, University of Leeds, United Kingdom. I am 27 and my research is Molecular Microbiology

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