DNA Vaccine

DNA Vacci accine ne 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 .

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Edward Jenner in 1798 used cowpox virus to immunize people against smallpox Smallpox

eradicatedOctober 1977: Last case (Somalia)

Edward Jenner 

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Killed and Attenuated Polio Vaccines

 Jonas

Salk: Killed Vaccine Salk:

 Albert

Sabin: Live Vaccine Sabin:

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Jonas Salk

Polio almost eradicated.

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.

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In 1992, scientists Tang and Johnson observed that mouse skeletal muscle can take up naked DNA and express proteins encoded by the DNA.

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Also they found that mice developed antibodies against the foreign protein (encoded by foreign DNA).

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Able to induced both Humoral immune response and Cell mediated immune response. response .

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Steps leading to immune response:

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Proteolytic degradation of foreign protein.

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Association of fragments with MHC class I and class II molecules

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Class I molecule present foreign protein synthesize within the cell while

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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.

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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.

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Injection of DNA using a standard hypodermic needle

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Gene gun delivery

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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.

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Ease of development and production.

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Stability of vaccine for storage and shipping .

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Cost-effectiveness-cold temperature storage accounts nearly Cost-effectiveness-cold 80% of the cost of vaccinating individuals in developing nations

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In vivo expression ensures protein more closely resembles re sembles normal eukaryotic structure, with accompanying posttranslational modifications

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Long-term persistence of immunogen.

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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 for non-protein based antigens such as bacterial polysaccharides.

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Risk of affecting genes controlling cell growth.

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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.

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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.

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August 2007 – DNA vaccine to protect horses from west nile virus was approved.

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Canada licensed first DNA vaccine for infectious haemopoetic necrosis virus in salmon.

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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.

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Clinical trials in present times will translate into clinical reality in future - in the form of vaccine against malaria etc.

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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