2. PREFACE
• What is a vaccine?
• Properties of good vaccine
• Types of vaccines
• Advantages of recombinant vaccines over
conventional vaccines
• Recombinant virus vaccines or live
recombinant vaccines
• Future Potential
• References
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 the particular
pathogen.
• Long term protection
• Safety
• Stability
• Inexpensiveness
6. Types of vaccines
• Live vaccines
• Killed or whole organism vaccines
• Subunit vaccines-purified or
recombinant antigen
• Recombinant vaccines
• DNA vaccines
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 of
time.
• For example typhoid vaccines.
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 or
semi-pure antigen.
These are of three types, toxoids,
recombinant subunit vaccines and non
recombinant 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 VACCINES (NON-RECOMBINANT)
• Constituent proteins of bacteria or virus are
isolated and purified
• Advantages:
• Defined Composition
• Various 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 Advantages Drawbacks
type
• Live vaccines 1.one or few doses 1.controlled attenuation
normally required required
2.Long term protection 2.risk of reversion
3.Both cellular and humoral 3.poorly defined
responses composition
• Killed vaccines 1.No risk of reversion 1.multiple doses
2.No risk of transmission required
2.poorly defined
composition
• Subunit vaccines 1.Defined composition 1.multiple doses
(non recombinant) 2.various delivery systems required
available 2.adjuvants needed
• Subunit vaccines 1.no risk of pathogenicity 1.multiple doses typically
(recombinant) 2.defined composition needed
3.various delivery systems 2.adjuvants needed
available
4.large scale production simplified
5.further genetic engineering possible
14. Which Vector to be used?
Must be compatible with host cell system
(prokaryotic vectors for prokaryotic cells,
eukaryotic vectors for eukaryotic cells)
Needs a good combination of
– strong promoters
– ribosome binding sites
– termination sequences
– affinity tag or solublization sequences
– multi-enzyme restriction site
15. A gene 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..
• Vaccines 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 vaccines
• Chemical or physical
inactivation(killed)
• Laboratory induced
changes to weaken
pathogens(live
attenuated)
• Isolate related and
designed attenuated (Live)
Recombinant DNA
vaccines
• Recombinant generated
subunits or DNA
vaccines(killed)
• Gene deleted
pathogens
• Vector-based organisms
to deliver foreign gene
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
• Vaccines developed for non-infectious agents: control and
prevent cancer; vaccines to induce long lasting contraception