All the basics about DNA Vaccones nd pathways of work. . .

1. Presented
By
Sumit Sharma
Raunak Prakash Asopa
Soarab Sharma
Mriganka Mandal

2. Contents
 Introduction
 DNA based
vaccines
 History
 Why
DNA vaccines
 How DNA vaccines made
 Methods of delivery
 Mechanism
 Advantages and Disadvantages
 Current clinical trials
 Future prospects

3. Introduction



A vaccine is a biological preparation that
improves immunity to a particular disease.
It contains an agent that resembles a
disease-causing microorganism, and is
often made from weakened or killed forms
of the microbe, its toxins or one of its
surface proteins.
The agent stimulates the body's immune
system to recognize the agent as foreign,
destroy it, and "remember" it, so that the
immune system can more easily recognize
and destroy any of these microorganisms
that it later encounters.

4. DNA based vaccines


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DNA vaccination is a technique for
protecting an organism against disease by
injecting it with genetically engineered
DNA to produce an immunological
response.
Circular double stranded DNA molecule,
referred to as a plasmid fabricated with
DNA sequence containing genes encoding
one or more proteins of a pathogen.
As this DNA inserted into cells it is
translated to form antigenic protein. As this
protein is foreign to cells , so immune
response raised against this protein.

5. History
 DNA vaccines
are third generation vaccines and are made
up of a small, circular piece of bacterial DNA
 In 1990, University of Wisconsin, Jon Wolff found that
injection of DNA plasmids produce a protein response in
mice.
 In 1993, Merck Research Laboratories, Dr. Margaret Liu
found that intramuscular injection of DNA from influenza
virus into mice produced complete immune response.
 In 1996, trials involving T-cell lymphoma, influenza &
herpes simplex virus were started.

6. Why DNA vaccines?
 Normal
vaccines having a
possible risk of the vaccine
being fatal. But in DNA
vaccines there is no need of
using
actual
infectious
organism.
 Normal
vaccines provide
primarily Humoral immunity.
On the other hand DNA
vaccines
provide
both
Humoral & Cell mediated
immunity.

7. DNA vaccine is made
Viral gene
Recombinant DNA
Technology
Expression plasmid
Plasmid with foreign gene

8. Transform in to bacteria
Plasmid DNA get Amplified

9. Plasmid DNA isolated
Stored in vials
Ready for Apply

10. Methods of delivery
 Injection:
Large amount of DNA
vaccines applied directly to the
skeletal tissues.
 Gene Gun: Small amount of vaccine
applied through DNA coated gold
beads to the abdominal skin.
 Pneumatic Jet Injection: Very high
amount of vaccine applied to the
abdominal skin.

11. Mechanism
BY TWO PATHWAYS
 ENDOGENOUS :Antigenic Protein is
presented by cell in which
it is produced.
 EXOGENOUS
:Antigenic Protein is formed
in one cell but presented by
different cell.

12. How DNA vaccines work
+
Muscle Cells
Plasmid DNA

13. Endogenous Pathway
Nucleus
Plasmid
DNA
MHC-I
mRNA
Antigenic
Protein
Antigenic
Peptides

14. T- Helper Cell
Memory T cells

15. Exogenous Pathway
Antigenic Protein come outside

16. Antigen Presenting Cell
Antigenic Peptides
T- Helper Cell
Memory
Antibodies
Cytokines
Plasma B-Cell
MHC-II
Activated B-Cell
Memory B-Cell

17. When Virus Enter in the Body
Memory T-Cell
Viral Protein
Antibodies

18. Advantages
 Vaccination
with no risk for infection.
 Antigen presentation by both MHC class I and class II
Molecules.
 Immune response focused only on antigen of interest.
 Stability of vaccine for storage and shipping
 Cost-effectiveness.
 Long-term persistence of immunogen.

19. Disadvantages
 Limited
to protein immunogens.
 Risk
of affecting genes controlling
cell growth.
 Possibility
of inducing antibody
production against DNA.
 Possibility
of tolerance to the
antigen (protein) produced.

20. Current clinical
trials

21. Review
Recent advance in immunotherapies for Alzheimer
disease (1999)

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DNA vaccination has been developed as a
new therapy for Alzheimer Disease
treatment.
Alzheimer disease (AD) is the most
common cause of dementia characterized
by progressive neurodegeneration.
An Adeno-assosiated Viral vector
developed by Zhang and his colleagues
could express Aβ in in-vivo condition.
They prepare DNA vaccine using this
AAV genome and tested on AD model
mice.

22. of Aβ burden in APP23 mice after DNA
vaccination is shown in the diagram. Prophylactic
administration of Fc-Aβ vaccine prevented the Aβ
deposition to 10–30% of that in untreated animals before
12 months of age and to 40–50% after 15 months (closed
triangles). The effects of therapeutic administration were
almost same as those of prophylactic administration.
 Reduction

23. Other clinical trials:
 June
2006,DNA vaccine examined on horse. Horse
acquired immunity against west nile viruses.
 August
2007,DNA vaccination against
Sclerosis was reported as being effective.
 In
multiple
Oct. 2011 DNA Vaccines Show Promise in
Preventing Dental Caries. DNA vaccine prepared using
recombinant flagellin protein derived from Salmonella
as mucosal adjuvant for anti-caries DNA vaccine.

24. Future prospects
 Plasmid
with multiple genes
provide immunity against many
diseases in one booster.
 DNA
vaccines
against
infectious diseases such as
AIDS, Rabies, Malaria can be
available.
 In future DNA vaccines can be
applied to boost up the immune
system.

25. References
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Grammatikos, Alexandros P.; (June 2009). "Meta-analyses on
Pediatric Infections and Vaccines". Infectious Disease Clinics of
North America 23 (2): 431–57.
Alarcon JB, Waine GW, McManus DP (1999). "DNA vaccines:
technology and application as anti-parasite and anti-microbial
agents". Adv. Parasitol. 42: 343–410.
Tang DC, DeVit M, Johnston SA. (1992)“Genetic immunization is a
simple method for eliciting an immune response”. Nature; 356:1524.
Barry MA, Lai WC, Johnston SA.(1995) “Protection against
mycoplasma infection using expression- library immunization”.
Nature; 377:632-5.