DNA VaccineCoding 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 eradicated- October 1977: Last case (Somalia)

Edward Jenner

Vaccines Represent one of the Greatest Success Stories in Biology Killed and Attenuated Polio

Vaccines

Jonas Salk: Killed VaccineAlbert 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).

Immune response raised by DNA vaccines

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.

Delivery methods

I. Injection of DNA using a standard hypodermic needle

II. Gene gun delivery

III. 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 post-translational 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 pre-clinical 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