DNA Based Vaccines

PresentedBy

Sumit SharmaRaunak Prakash Asopa

Soarab SharmaMriganka Mandal

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

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.

DNA based vaccines 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.

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.

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.

DNA vaccine is made

Viral gene

Recombinant DNA Technology

Expression plasmid

Plasmid with foreign gene

Transform in to bacteria

Plasmid DNA get Amplified

Plasmid DNA isolated

Stored in vials

Ready for Apply

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.

MechanismBY 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.

How DNA vaccines work

Muscle Cells Plasmid DNA

+

mRNA

Antigenic Protein

Antigenic Peptides

MHC-I

Plasmid DNA

Nucleus

Endogenous Pathway

Multiply

Memory T cells

T- Helper Cell

Exogenous Pathway

Antigenic Protein come outside

Phagocytosed

Antigen Presenting Cell

Antigenic Peptides

T- Helper Cell

Cytokines

Activated B-Cell Memory B-Cell

Plasma B-Cell

Memory Antibodies

MHC-II

When Virus Enter in the Body

Viral Protein

Memory T-Cell

Antibodies

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.

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.

Current clinical trials

ReviewRecent advance in immunotherapies for Alzheimer disease (1999)

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.

Reduction 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.

June 2006,DNA vaccine examined on horse. Horse acquired immunity against west nile viruses.

August 2007,DNA vaccination against multiple Sclerosis was reported as being effective.

In 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.

Other clinical trials:

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.

References 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; 356:152-4.

Barry MA, Lai WC, Johnston SA.(1995) “Protection against mycoplasma infection using expression- library immunization”. Nature; 377:632-5.

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