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PRESENTED BY
B.KARTHIKEYAN
CONTENTS

   Introduction                 Advantages
   History                      Disadvantages
   DNA vaccines Vs              Clinical trials
    Traditional vaccines
   How DNA vaccine is made
                                 Safety issues
   Methods of delivery          Future of DNA
   How DNA vaccine works         vaccines
                                 Conclusion
                                 References
INTRODUCTION
   DNA vaccine is DNA sequence used as a
    vaccine.
   This DNA Sequence code for antigenic protein of
    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.
   In this way ,DNA vaccine provide immunity
    against that pathogen.
HISTORY
•   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 influenzae virus into mice produced
    complete immune response

•   In 1996, trials involving T-cell lymphoma,
    influenzae & herpes simplex virus were started
DNA vaccines Vs Traditional
vaccines

    DNA vaccines               Traditional vaccines
»    Uses only the DNA         »   Uses weakened or
     from infectious               killed form of infectious
     organisms.                    organism.
»    Avoid the risk of using   »   Create possible risk of
     actual infectious             the vaccine being fatal.
     organism.
»    Provide both Humoral      »   Provide primarily
     & Cell mediated               Humoral immunity
     immunity                  »   Usually requires
»    Refrigeration is not          Refrigeration.
HOW DNA VACCINE IS
         MADE
Viral gene

 Recombinant DNA
 Technology
                                         Expression
                                          plasmid




             Plasmid with foreign gene
Transform into
          bacterial cell




Plasmid
DNA
                    Bacterial cell
Plasmid DNA get
Amplified
Plasmid DNA
Purified




Ready to use
METHODS OF DELIVERY

Syringe delivery:-
                          Either
                     intramuscularly
                           or
                      Intradermally
Contd..

Gene gun delivery:-
                      Adsorbed plasmid DNA
                       into gold particles
                      Ballastically accelerated
                       into body with gene gun.
HOW DNA VACCINE WORKS

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
HOW DNA VACCINES
           WORK




               +
Muscle Cells       Plasmid DNA
ENDOGENOUS PATHWAY

Nucleus

Plasmid
DNA



 mRNA                  MHC-I


                               Antigenic
                               Peptides

           Antigenic
           Protein
T- Helper Cell
Mu
   lt   ipl
           y


                                Memory T cells
EXOGENOUS PATHWAY




              Antigenic Protein come outside
s ed
                 oc   yto
             g
         Pha

          Antigen Presenting Cell

                 Antigenic Peptides
                                                               Memory
                       T- Helper Cell
                                                               Antibodies
                          Cytokines
                                               Plasma B-Cell




MHC-II
                                Activated B-Cell      Memory B-Cell
WHEN VIRUS ENTER IN THE BODY




                           Memory T-Cell


                          Viral Protein



                           Antibodies
ADVANTAGES

*   Elicit both Humoral & cell mediated
    immunity
*   Focused on Antigen of interest
*   Long term immunity
*   Refrigeration is not required
*   Stable for storage
DISADVANTAGES

 Limited to protein immunogen only
 Extended immunostimulation leads
  to chronic inflammation
o Some antigen require processing
  which sometime does not occur
CLINICAL TRIALS

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
Genetic Toxicity
Integration of DNA vaccine into host Genome


           Insertional mutagenesis
           Chromosome instability
            Turn ON Oncogenes
            Turn OFF Tumor suppressor genes
Over Expression of DNA vaccine

  Acute or chronic inflammatory responses

  Destruction of normal tisues
Generation of Autoimmune
diseases
   Anti DNA Antibodies

   Autoimmune diseases

   Autoimmune Myositis
Antibiotic Resistance

 Plasmid used is resistance to
  antibiotics for selection

 Raise the resistance to same
antibiotic in the host
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
CONCLUSION

* DNA vaccines are in their early phase.
* There are no DNA vaccines in market at
    present.
* But this just the beginning .
* DNA vaccines are going to be the vaccines of
     next generation.
References

>   www.medscape.com
>   www.wikipedia.org
>   www.sciencedirect.com
>   www.nature.com
>   www.biokenyon.com
>   www.biolife.com
   Immunology by Kuby 6th Edition
   Immunology by Tizard 4th Edition
THANK YOU

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DNA vacccine

  • 2. CONTENTS  Introduction  Advantages  History  Disadvantages  DNA vaccines Vs  Clinical trials Traditional vaccines  How DNA vaccine is made  Safety issues  Methods of delivery  Future of DNA  How DNA vaccine works vaccines  Conclusion  References
  • 3. INTRODUCTION  DNA vaccine is DNA sequence used as a vaccine.  This DNA Sequence code for antigenic protein of 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.  In this way ,DNA vaccine provide immunity against that pathogen.
  • 4. HISTORY • 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 influenzae virus into mice produced complete immune response • In 1996, trials involving T-cell lymphoma, influenzae & herpes simplex virus were started
  • 5. DNA vaccines Vs Traditional vaccines DNA vaccines Traditional vaccines » Uses only the DNA » Uses weakened or from infectious killed form of infectious organisms. organism. » Avoid the risk of using » Create possible risk of actual infectious the vaccine being fatal. organism. » Provide both Humoral » Provide primarily & Cell mediated Humoral immunity immunity » Usually requires » Refrigeration is not Refrigeration.
  • 6. HOW DNA VACCINE IS MADE Viral gene Recombinant DNA Technology Expression plasmid Plasmid with foreign gene
  • 7. Transform into bacterial cell Plasmid DNA Bacterial cell
  • 10. METHODS OF DELIVERY Syringe delivery:- Either intramuscularly or Intradermally
  • 11. Contd.. Gene gun delivery:- Adsorbed plasmid DNA into gold particles Ballastically accelerated into body with gene gun.
  • 12. HOW DNA VACCINE WORKS 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
  • 13. HOW DNA VACCINES WORK + Muscle Cells Plasmid DNA
  • 14. ENDOGENOUS PATHWAY Nucleus Plasmid DNA mRNA MHC-I Antigenic Peptides Antigenic Protein
  • 15. T- Helper Cell Mu lt ipl y Memory T cells
  • 16. EXOGENOUS PATHWAY Antigenic Protein come outside
  • 17. s ed oc yto g Pha Antigen Presenting Cell Antigenic Peptides Memory T- Helper Cell Antibodies Cytokines Plasma B-Cell MHC-II Activated B-Cell Memory B-Cell
  • 18. WHEN VIRUS ENTER IN THE BODY Memory T-Cell Viral Protein Antibodies
  • 19. ADVANTAGES * Elicit both Humoral & cell mediated immunity * Focused on Antigen of interest * Long term immunity * Refrigeration is not required * Stable for storage
  • 20. DISADVANTAGES  Limited to protein immunogen only  Extended immunostimulation leads to chronic inflammation o Some antigen require processing which sometime does not occur
  • 21. CLINICAL TRIALS 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
  • 22.
  • 23. Genetic Toxicity Integration of DNA vaccine into host Genome Insertional mutagenesis Chromosome instability Turn ON Oncogenes Turn OFF Tumor suppressor genes
  • 24. Over Expression of DNA vaccine Acute or chronic inflammatory responses Destruction of normal tisues
  • 25. Generation of Autoimmune diseases Anti DNA Antibodies Autoimmune diseases Autoimmune Myositis
  • 26. Antibiotic Resistance  Plasmid used is resistance to antibiotics for selection  Raise the resistance to same antibiotic in the host
  • 27. 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
  • 28. CONCLUSION * DNA vaccines are in their early phase. * There are no DNA vaccines in market at present. * But this just the beginning . * DNA vaccines are going to be the vaccines of next generation.
  • 29. References > www.medscape.com > www.wikipedia.org > www.sciencedirect.com > www.nature.com > www.biokenyon.com > www.biolife.com  Immunology by Kuby 6th Edition  Immunology by Tizard 4th Edition