DNA Vaccines

1
DNA Vaccines

• Jessica El-beck
• May 1st 2007

2
Overview

• History of vaccines
• Discovery of DNA vaccines
• What Are DNA vaccines
• Immune Response
• Advantages and limitation
• Examples
• Conclusions

3
History of Vaccines

• The 1st vaccine was developed in 1796
• It is estimated that of the 30 years added to
  average human life span in the 20th century,
  10-15 years have resulted from vaccination.
• Vaccine is a non-disease causing mimic of an
  infectious agent.

4
History of Vaccines

• Successful vaccination protects both individuals
  and populations.
• Vaccination were responsible for eradicating
  diseases such as polio, small pox and measles in
  the developed nations.
• Details of how they worked were not known

5
History of Vaccines

• Rational approach in vaccine development
• Inoculation of one or more proteins
• 8-12 amino acids in a pathogenic protein are
  sufficient to evoke an immune response

6
Modern Vaccines Problems

• Require expensive virus/protein purification
  techniques
• Cold storage facilities
• Many vaccine preventable diseases continue to
  remain major health hazards in developing
  nations.
• Urgent need to develop safe, inexpensive and room
  temperature-storable

7
Discovery of DNA vaccines

• DNA vaccines where discovered by accident
• Published in Science in 1993
• It was observed that mouse skeletal muscle can
  take up naked DNA and express proteins encoded by
  the DNA.

8
Discovery of DNA vaccines

• DNA encoding an influenza virus protein was
  injected into the skeletal muscle of mice
• Synthesis of the virus protein in the mouse
  muscle triggered an immune response
• Resulting in protection of the mice from a
  subsequent influenza infection.

9
Discovery of DNA Vaccines

• DNA vaccines have been explored for a number of
  viral, bacterial, and parasitic diseases.

10
What Are DNA Vaccines?

• DNA vaccines are a circular double stranded DNA
  molecule
• Plasmid are of bacterial origin
• Plasmids can be isolated from bacteria simply and
  inexpensively

11
What Are DNA Vaccines?

• Using recombinant DNA techniques, it is possible
  to insert a foreign gene into the plasmid
  molecule to generate a recombinant plasmid

12
How DNA Vaccines Work

• Plasmids are introduced into eukaryotic cells
• The gene of interest is transcribed by the RNA
  polymerase II
• mRNA is than translated into the corresponding
  protein in the cytoplasm of the host cells.

13
Antigen presentation

• Proteolytic degradation of the foreign proteins
• Association of the proteolytic fragments with two
  different types of major histocompatibility
  complex (MHC)
• Both of these present proteolytically degraded
  fragments of proteins to T-cells

14
Immune response

• Class I molecules present fragments of proteins
  to cytotoxic T-cells
• Class II molecules present protein fragments to
  T-helper cells
• Since the pathogenic proteins are synthesized
  inside the host cells, both humoral and
  cell-mediated immune responses can be induced.

15
Immune Response
16
Immune Response
17
Advantages

• Vaccine failure is limited because protein is
  synthesized in its native form inside the host
  cell
• Non-infectious
• Economical to produce
• Easy to purify

18
Advantages

• DNA vaccines do not require a cold-chain
• DNA vaccine plasmids can be constructed using
  simple recombinant DNA techniques
• Possible to make DNA vaccines that can protect
  against multiple pathogen

19
Limitations

• Can only induce immune responses against the
  protein components of the pathogen
• Mechanism not completely understood
• Unresponsiveness, rather than protective
  immunity, might result

20
Limitations

• Plasmid DNA integrating into the genome randomly
  might cause insertional mutagenesis
• Induction of anti-DNA antibodies by plasmid DNA

21
Administration
22
The Gene Gun

• Modern way to deliver genetic vaccines
• Quickly shoots DNA that has been coated into
  ultra small gold beads
• Penetrates the skin with no discomfort

23
Influenza

• The 1st disease for which immunity was
  demonstrated
• The lack of vaccine that provides life-long
  immunity against all strains of influenza is a
  major healthcare problem
• Studies have shown that DNA vaccines based on one
  strain of influenza could protect against a
  different strain

24
Influenza

• The 1st human trail of a DNA vaccine designed to
  prevent avian influenza began in December 2006
• 45 volunteers between the ages of 18 and 60 will
  receive 3 injections over 2 months
• The vaccine is a modified version of the
  hemagglutinin gene

25
West Nile Virus

• Vaccines 1st used on Condors and Crows
• Experimental recombinant DNA vaccine was used in
  an effort to protect endangered condors in
  California zoos.
• A study of infected crows found that an
  experimental DNA vaccine reduced mortality rates
  by 60.
• Manufacture of an oral vaccine for use on wild
  birds is being investigated by government
  researchers in collaboration with scientists at
  several universities.

26
West Nile Virus

• The USDA granted the 1st license for DNA vaccines
  for horses on July 8th 2005
• This was the 1st DNA vaccine for commercial sale
• This vaccine has proven safe, potent,
• and effective

27
West Nile Virus

• Human trials are in phase 1 cinical trails
• 15 volunteers will receive three injections with
  a needle-free injector about 4 weeks apart
• They will be monitored for 32 weeks for side
  effects and for WNV-specific antibodies and T
  cells.

28
AIDS and DNA Vaccines

• Several experimental DNA vaccines for HIV/AIDS
  have been produced and tested in small animals
  and non-human primates with promising results
• DNA vaccines delivered intramuscularly or by gene
  gun have been shown to induce both neutralizing
  antibodies and CTL responses against HIV

29
AIDS and DNA Vaccines

• For the past six years, scientists have been
  evaluating DNA vaccines.
• An initial clinical study of a multiclade,
  multigene DNA vaccine developed by VRC
  demonstrated that it was safe, well-tolerated,
  and frequently induced human HIV-specific immune
  responses.

30
Conclusions

• DNA Vaccines hold promise for the future for
  vaccinations
• Eliminate problems associated with current
  vaccines
• Still being understood

31
Conclusions

• Clinical trails are underway for several DNA
  vaccines
• Could protect Humans and animals from disease
  that currently do not have vaccines
• Might be the answer to ADIS vaccines

32
References

• Donnelly, J. J. Ulmer, J. B. Shiver, J. W. Liu
  M. A. Annu. Rev. Immunol. 1997, 15, 617.
• McMichael, A. J. Annu. Rev. Immunol. 2006, 24,
  227.
• McDonnell, W. M. Askari, F. K. The Emerging Role
  of DNA Vaccines. Medscape General Medicine
  Online 1999, 1(3).
• Rangarajan, P. N. Resonance. 2002, 25.

33
Questions?