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 eradicated-
October 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

Jonas Salk
 Albert Sabin: Live Vaccine

 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

Fig: Vector plasmid having
future of DNA molecule antigen encoding gene.
for immunization.
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 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