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RECOMBINANT
V
ACCINES
PREFACE
What is a vaccine?
Properties of good vaccine
Types of vaccines
Advantages of recombinant
conventional vaccines
Recombinant virus vaccines
recombinant vaccines
Future Potential
References
•
•
•
• vaccines over
• or live
•
•
WHAT IS A VACCINE?
A preparation of killed or weakened microorganism that is
given to a person orally or injected in order to prevent
disease.
• Edward Jenner demonstrated that a person inoculated
into the skin with cowpox was protected against small
pox and he thus developed the principles of vaccination
in 1796.
In 1881 Louis Pasteur honored Jenner by naming the
processing ‘’vaccination’’ and the substance used to
vaccinate was a ‘’vaccine’’.
•
• Principle of a vaccine is to induce a primary
response in the vaccinated subject so that
following the exposure of a pathogen,a rapid
secondary immune response is generated
leading to accelerated elimination of the
organism and protection from clinical disease.
Success depends on the generation of memory
T cells and B cells and presence of
neutralizing antibody serum.
•
Properties of a good vaccine
• Ability to elicit the appropriate
immune response for
pathogen.
the particular
•
•
•
•
Long term
Safety
Stability
protection
Inexpensiveness
Types
• Live vaccines
of vaccines
• Killed or whole organism vaccines
• Subunit vaccines-purified or
recombinant antigen
• Recombinant vaccines
• DNAvaccines
These vaccines are prepared from attenuated strains
that are almost or completely devoid of
pathogenicity but are capable of inducing a
protective immune response to the body.
They multiply in human host and provide
•
•
continuous antigenic stimulation over a period
time.
For example typhoid vaccines.
of
•
Killed whole organism vaccines
• It is a vaccine that is produced by growing the
organism and then killing or inactivating it
with heat and/or chemicals.
• These are used when safe live vaccines are not
available
• For example inactivated polio vaccine
• Rabies vaccine
 Subunit vaccines are defined as those
vaccines containing one or more pure
semi-pure antigen.
or
 These are of
recombinant
recombinant
three types, toxoids,
subunit vaccines and non
subunit vaccines.
Toxoids
• In some diseases like diphtheria and tetanus it is
not the growth of the bacterium that is dangerous,
but the protein toxin that is liberated by it.
• Treating the toxin with formaldehyde denatures
the protein so that it is no longer dangerous.
• The inactivated toxin is called as toxoid.
• For example, DPT vaccine also called as triple
vaccine.
• SUBUNIT V
ACCINES (NON-RECOMBINANT)
• Constituent proteins of bacteria or virus are
isolated and purified
• Advantages:
• Defined Composition
• V
arious delivery systems available
• Disadvantages:
• Antigens must be produced and purified by
cultivation of a pathogen
• Multiple doses typically required
• Adjuvant needed
Subunit recombinant vaccines
These vaccines are those in which genes for desired antigens are inserted
into a vector, usually a virus, that has a very low virulence.
The vector expressing the antigen may be used as the vaccine, or the antigen
may be purified and injected as a subunit vaccine.
The only recombinant vaccine currently in use in humans is the Hepatitis B
Virus (HBV) vaccine, which is a recombinant subunit vaccine
Hepatitis B surface antigen is produced from a gene transfected into yeast
cells and purified for injection as a subunit vaccine.
This is much safer than using attenuated HBV, which could cause lethal
hepatitis or liver cancer if it reverted to its virulent phenotype.
Recombinant DNA techniques can also be used to make safer attenuated
pathogen vaccines
Vaccine
type
Live vaccines
Advantages Drawbacks
• 1.one or few doses
normally required
2.Long term protection
3.Both cellular and humoral
responses
1.controlled attenuation
required
2.risk of reversion
3.poorly defined
composition
• Killed vaccines 1.No risk of reversion
2.No risk of transmission
1.multiple doses
required
2.poorly defined
composition
• Subunit vaccines 1.Defined composition
2.various delivery systems
available
1.multiple doses
required
2.adjuvants needed
(non recombinant)
• Subunit vaccines 1.no risk of pathogenicity
2.defined composition
3.various delivery systems
available
4.large scale production simplified
5.further genetic engineering possible
1.multiple doses typically
needed
2.adjuvants needed
(recombinant)
Which Vector to be used?
Must be compatible with host cell system
(prokaryotic vectors for prokaryotic cells,
eukaryotic vectors for eukaryotic
Needs a good combination of
cells)
–
–
–
–
–
strong promoters
ribosome binding sites
termination sequences
affinity tag or solublization sequences
multi-enzyme restriction site
 Agene coding for an immunogenic protein from
one organism into the genome of other, such as
vaccinia virus is introduced.
 The organism expressing that gene is called as
recombinant.
 Following injection into the subject, the
recombinant will replicate and express sufficient
amounts of the foreign protein to induce a specific
immune response to the protein.
Advantages of viral vector
vaccines
Elicit strong humoral and cell-mediated immune
responses, resulting in immunological memory.
Can be targeted by viral tropisms for particular cells,
e.g. intestine, brain, etc., inducing desired immunity.
Can also encode for several antigens from different
pathogens, introducing the possibility of a single
vaccine for several diseases.
•
•
•
• Viral vectors have been found not to interfere with the
protection produced by other types of vaccines..
V
accines are relatively inexpensive and, for some,
easily transportable.
•
Disadvantages
• Since the live virus being used is an attenuated form of a
human pathogen, there is always a risk of reversion to
virulence.
Some of the vectors under consideration, such as adenovirus,
•
have the capability of transforming cells to a cancerous
phenotype. While these oncogenes are removed, vector virus
could recombine with naturally occurring, pathogenic strains
in the environment and form a new hybrid virus with
transforming properties.
• Immune response to virus-infected cells may cause
pathological problems.
Conventional vs Recombinant DNA
Vaccines
Conventional
Recombinant DNA
vaccines
vaccines
• •
Chemical or physical
inactivation(killed)
Laboratory induced
changes to weaken
pathogens(live
attenuated)
Isolate related and
Recombinant generated
subunits or DNA
vaccines(killed)
Gene deleted
pathogens
Vector-based organisms
to deliver foreign gene
•
•
•
•
designed attenuated (Live) products(Live)
Future Developments
• Identification and utilization of better immunogens as new
vaccines for diseases
• Better vaccine delivery methods: oral, intranasal, and
systems allowing mass vaccinations
• Use of immunomodulators in vector-based vaccines: CPG
motifs and cytokines.
• Expression of foreign proteins in plants and the development
of edible vaccines
• V
accines developed for non-infectious agents: control and
prevent cancer; vaccines to induce long lasting contraception
References
Sciencedirect.com
Academia.com
Animal Agriculture's Future through
Biotechnology- Mark W
. Jackwood, Leslie
Hickle
•
•
•
• Essentials of Clinical
Hoffbrand
Immunology-A.V
Thanx a lot

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recombinant vaccines.pptx

  • 2. PREFACE What is a vaccine? Properties of good vaccine Types of vaccines Advantages of recombinant conventional vaccines Recombinant virus vaccines recombinant vaccines Future Potential References • • • • vaccines over • or live • •
  • 3. WHAT IS A VACCINE? A preparation of killed or weakened microorganism that is given to a person orally or injected in order to prevent disease. • Edward Jenner demonstrated that a person inoculated into the skin with cowpox was protected against small pox and he thus developed the principles of vaccination in 1796. In 1881 Louis Pasteur honored Jenner by naming the processing ‘’vaccination’’ and the substance used to vaccinate was a ‘’vaccine’’. •
  • 4. • Principle of a vaccine is to induce a primary response in the vaccinated subject so that following the exposure of a pathogen,a rapid secondary immune response is generated leading to accelerated elimination of the organism and protection from clinical disease. Success depends on the generation of memory T cells and B cells and presence of neutralizing antibody serum. •
  • 5. Properties of a good vaccine • Ability to elicit the appropriate immune response for pathogen. the particular • • • • Long term Safety Stability protection Inexpensiveness
  • 6. Types • Live vaccines of vaccines • Killed or whole organism vaccines • Subunit vaccines-purified or recombinant antigen • Recombinant vaccines • DNAvaccines
  • 7. These vaccines are prepared from attenuated strains that are almost or completely devoid of pathogenicity but are capable of inducing a protective immune response to the body. They multiply in human host and provide • • continuous antigenic stimulation over a period time. For example typhoid vaccines. of •
  • 8. Killed whole organism vaccines • It is a vaccine that is produced by growing the organism and then killing or inactivating it with heat and/or chemicals. • These are used when safe live vaccines are not available • For example inactivated polio vaccine • Rabies vaccine
  • 9.  Subunit vaccines are defined as those vaccines containing one or more pure semi-pure antigen. or  These are of recombinant recombinant three types, toxoids, subunit vaccines and non subunit vaccines.
  • 10. Toxoids • In some diseases like diphtheria and tetanus it is not the growth of the bacterium that is dangerous, but the protein toxin that is liberated by it. • Treating the toxin with formaldehyde denatures the protein so that it is no longer dangerous. • The inactivated toxin is called as toxoid. • For example, DPT vaccine also called as triple vaccine.
  • 11. • SUBUNIT V ACCINES (NON-RECOMBINANT) • Constituent proteins of bacteria or virus are isolated and purified • Advantages: • Defined Composition • V arious delivery systems available • Disadvantages: • Antigens must be produced and purified by cultivation of a pathogen • Multiple doses typically required • Adjuvant needed
  • 12. Subunit recombinant vaccines These vaccines are those in which genes for desired antigens are inserted into a vector, usually a virus, that has a very low virulence. The vector expressing the antigen may be used as the vaccine, or the antigen may be purified and injected as a subunit vaccine. The only recombinant vaccine currently in use in humans is the Hepatitis B Virus (HBV) vaccine, which is a recombinant subunit vaccine Hepatitis B surface antigen is produced from a gene transfected into yeast cells and purified for injection as a subunit vaccine. This is much safer than using attenuated HBV, which could cause lethal hepatitis or liver cancer if it reverted to its virulent phenotype. Recombinant DNA techniques can also be used to make safer attenuated pathogen vaccines
  • 13. Vaccine type Live vaccines Advantages Drawbacks • 1.one or few doses normally required 2.Long term protection 3.Both cellular and humoral responses 1.controlled attenuation required 2.risk of reversion 3.poorly defined composition • Killed vaccines 1.No risk of reversion 2.No risk of transmission 1.multiple doses required 2.poorly defined composition • Subunit vaccines 1.Defined composition 2.various delivery systems available 1.multiple doses required 2.adjuvants needed (non recombinant) • Subunit vaccines 1.no risk of pathogenicity 2.defined composition 3.various delivery systems available 4.large scale production simplified 5.further genetic engineering possible 1.multiple doses typically needed 2.adjuvants needed (recombinant)
  • 14. Which Vector to be used? Must be compatible with host cell system (prokaryotic vectors for prokaryotic cells, eukaryotic vectors for eukaryotic Needs a good combination of cells) – – – – – strong promoters ribosome binding sites termination sequences affinity tag or solublization sequences multi-enzyme restriction site
  • 15.  Agene coding for an immunogenic protein from one organism into the genome of other, such as vaccinia virus is introduced.  The organism expressing that gene is called as recombinant.  Following injection into the subject, the recombinant will replicate and express sufficient amounts of the foreign protein to induce a specific immune response to the protein.
  • 16. Advantages of viral vector vaccines Elicit strong humoral and cell-mediated immune responses, resulting in immunological memory. Can be targeted by viral tropisms for particular cells, e.g. intestine, brain, etc., inducing desired immunity. Can also encode for several antigens from different pathogens, introducing the possibility of a single vaccine for several diseases. • • • • Viral vectors have been found not to interfere with the protection produced by other types of vaccines.. V accines are relatively inexpensive and, for some, easily transportable. •
  • 17. Disadvantages • Since the live virus being used is an attenuated form of a human pathogen, there is always a risk of reversion to virulence. Some of the vectors under consideration, such as adenovirus, • have the capability of transforming cells to a cancerous phenotype. While these oncogenes are removed, vector virus could recombine with naturally occurring, pathogenic strains in the environment and form a new hybrid virus with transforming properties. • Immune response to virus-infected cells may cause pathological problems.
  • 18.
  • 19. Conventional vs Recombinant DNA Vaccines Conventional Recombinant DNA vaccines vaccines • • Chemical or physical inactivation(killed) Laboratory induced changes to weaken pathogens(live attenuated) Isolate related and Recombinant generated subunits or DNA vaccines(killed) Gene deleted pathogens Vector-based organisms to deliver foreign gene • • • • designed attenuated (Live) products(Live)
  • 20. Future Developments • Identification and utilization of better immunogens as new vaccines for diseases • Better vaccine delivery methods: oral, intranasal, and systems allowing mass vaccinations • Use of immunomodulators in vector-based vaccines: CPG motifs and cytokines. • Expression of foreign proteins in plants and the development of edible vaccines • V accines developed for non-infectious agents: control and prevent cancer; vaccines to induce long lasting contraception
  • 21. References Sciencedirect.com Academia.com Animal Agriculture's Future through Biotechnology- Mark W . Jackwood, Leslie Hickle • • • • Essentials of Clinical Hoffbrand Immunology-A.V