DNA Vaccine

Coding for prevention……. Coding against immunity……

What are vaccines?????
 Vaccine is an attenuated form of disease causing organism, able to stimulate the immune response; without subjecting the individual to the risk of actual infection.

 Edward Jenner in 1798 used cowpox virus to immunize people against smallpox Smallpox eradicatedOctober 1977: Last case (Somalia)

Edward Jenner

Vacc in es R eprese nt o ne of the Grea test Succe ss St or ies in B iol ogy
 Killed and Attenuated Polio Vaccines  Jonas Salk: Killed Vaccine  Albert Sabin: Live Vaccine  Polio almost eradicated.

Jonas Salk

Albert Sabin

Evolution of Vaccines

DNA vaccine
• DNA vaccine is a circular double stranded DNA Molecule {referred to as a plasmid} containing genes encoding one or more proteins of a pathogen. • Basis for the scientific future of DNA molecule for immunization.

Fig: Vector plasmid having antigen encoding gene.

Chance discovery…
• Many discoveries occurred as serendipitous discoveries, same is the case with DNA vaccines. • In 1992, scientists Tang and Johnson observed that mouse skeletal muscle can take up naked DNA and express proteins encoded by the DNA. • Also they found that mice developed antibodies against the foreign protein (encoded by foreign DNA).

Imm un e r esp on se r aise d by DNA v ac ci nes
 Able to induced both Humoral immune response and Cell mediated immune response.  Steps leading to immune response:  Proteolytic degradation of foreign protein.  Association of fragments with MHC class I and class II molecules  Class I molecule present foreign protein synthesize within the cell while  Class II molecule present foreign protein synthesized within the cell as well as taken from outside through endocytosis

Cont…
Antigen is synthesized within the cells so both class I and II molecules present it.  Class I molecule induce Cytotoxic t cell response while Class II molecule induce humoral immune response . 

Hence antibody producing B-cell and cytotoxic T-cell mediated immune response are raised.

Deli ve ry me tho ds
• Injection of DNA using a standard hypodermic needle

Gene gun delivery

Aerosol instillation of naked DNA on mucosal surfaces, such as the nasal and lung mucosa

Advantages
 Able to polarise T-cell help toward type 1 or type 2.  Ease of development and production.  Stability of vaccine for storage and shipping .  Cost-effectiveness-cold temperature storage accounts nearly 80% of the cost of vaccinating individuals in developing nations  In vivo expression ensures protein more closely resembles normal eukaryotic structure, with accompanying posttranslational modifications

 Long-term persistence of immunogen.  Vaccines for multiple diseases can all be given in a single inoculation. Currently, the full course of childhood immunizations requires 18 visits to the doctor or clinic, in developed nations.

Limitations
• Not useful for non-protein based antigens such as bacterial polysaccharides. • Risk of affecting genes controlling cell growth. • Possibility of inducing antibody production against DNA - are specific for the DNA of that particular bacterial species and do not cross-react with mammalian DNA. • Potential for insertional mutagenesis in organism -studies have found that rate of mutation was 3000 times less than the spontaneous mutation rate for mammalian genomes.

A Comparison

Kube ; Immunology, Fifth edition

DNA vaccines in stores
• In June 2006 positive results were announced for bird flu DNA vaccine. • August 2007 – DNA vaccine to protect horses from west nile virus was approved. • Canada licensed first DNA vaccine for infectious haemopoetic necrosis virus in salmon. • DNA vaccine expressing human tyrosin as encoding gene to enhance long-term survival in canine malignant melanoma

Future prospects
• Careful evaluation of the safety of DNA vaccines in preclinical and then clinical studies. • Clinical trials in present times will translate into clinical reality in future - in the form of vaccine against malaria etc. • Use of genome sequence data of several pathogenic microbes to develop genomic vaccines through expression library immunization

While the potential benefits of DNA

vaccines are enormous, the media should inform the public about DNA vaccine research with cautious optimism. People should broaden their perspective to accept DNA vaccines as a major tool for eradication of diseases

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