2. HISTORICAL PERSPECTIVES
2
Jenner 1796 : Cowpox
• 1800’s Compulsory
childhood vaccination
• 1930’s Last natural UK
case
• 1940’s last natural US case
• 1958 WHO program
• October 1977: Last case
(Somalia)
4. Active Vs Passive Immunization
Active immunization
Can be achieved through natural infection by a
microorganism or it can be acquired artificially
through the administration of vaccines
Antibodies produced in response to an
infection e.g. natural measles virus
Antibodies produced in response to a vaccine
(live, inactivated or toxoid)
Individuals make their own antibodies
5. Active Vs Passive Immunization
Passive Immunity
Individual gains antibodies from another
who has produced them
Transfer of maternal antibodies through the
placenta or in breast milk
Administration of antibodies collected from
actively immune humans or animals e.g.
varicella zoster immunoglobulin VZIG
7. What is a Vaccine?
A preparation of the causative agent of a
disease, specially treated for use in vaccination,
in order to induce or increase immunity
Typically contains an agent that resembles a
disease-causing microorganism, and is often
made from Weakened or killed microorganisms
or subunits (purified protein subunits,
polysaccharides).
8. What is a Vaccine?
Based on 2 key elements of adaptive
immunity:
Specificity and Memory
Stimulation of an individual’s own
immune system to produce antibodies by
administration of a vaccine
9. Active Immunization through
designing Vaccines
9
Before designing any vaccine, two things
should be considered:
Activation of humoral and cell mediated
immune response shown by a particular
antigen
Development of immunologic memory
by the particular antigen
10. The Mechanism of a Vaccine
In an ideal scenario,
whenever a vaccine is first
administered, it is
phagocytized by an antigen
presenting cell.
Recent research suggest
that it is particularly
important that the vaccine
be taken up by a dendritic
cell.
This is because dendritic
cells play a key role in
activating T cells, which
become helper T cells
11. From there, the
activated Th cells goes
on to activate mature
B-cells.
These activated B-cells
divides into two cell
types, antibody-
producing plasma cells
and, most importantly,
memory B cells.
The Mechanism of a
Vaccine
12. Importance of Secondary Immune
Response
During the secondary immune response, the body
mounts a quicker, more robust attack on the
pathogen.
Thus, the pathogen is cleared from the body
before it has the chance to cause an infection.
13. Adjuvants
An adjuvant is a
chemical substance that
can be added to a
vaccine in order to
enhance the immune
response to the vaccine.
There are three types of
adjuvants.
14. Adjuants
Aluminum Hydroxide and Aluminum Phosphate (Alum)
Alum is an inorganic salt that
binds to proteins and causes
them to precipitate.
Whenever the alum/vaccine
complex is injected into the
body, it slowly dissolves,
releasing the vaccine.
Bacterial extracts can be added,
which enhances the immune
response.
Alum is the only adjuvant
approved for use in humans.
15. Adjuants
Freund’s Adjuvant
In Freund’s adjuvant, the
vaccine is suspended in oil
droplets.
When injected into the body,
the vaccine slowly diffuses out
of the oil drop.
Bacterial antigens can be added
in order to enhance the immune
response.
Not used in humans because of
risk of severe inflammation.
16. Routes of Administration
There are three different routes
of administration:
Intradermal administration.
Three types are intravenous,
intramuscular, and
subcutaneous.
Oral administration.
Vaccine is usually given in
liquid form.
Foods, such as tomatoes, have
been engineered to produce a
vaccine.
Intranasal administration.
17. Boosters
For most vaccines, the
immunity against a particular
pathogen has a tendency
to wear off over time.
In this case, a periodic
“booster” administration must
be given in order to
strengthen and lengthen
the duration of immunity.
18. Active immunization by
artificial means can be achieved
by:18
Attenuated organisms (avirulent)
Inactivated organisms (killed)
Purified microbial macromolecules
Cloned microbial antigens
Synthetic peptides
Anti-idiotype antibodies
Multivalent complexes
22. Advantages of Attenuated Vaccines
22
•
•Raises immune response to all protective
antigens.
• More durable immunity
• Low cost
• Quick immunity in majority of vaccinees
• In case of polio and adeno vaccines, easy
administration
• Easy transport in field
•Disadvantages of Attenuated Vaccines
Mutation; reversion to virulence (often frequent)
24. Inactivated vaccines
The bacteria or
virus is completely
killed using a
chemical, usually
formaldehyde
Examples
hepatitis A
hepatitis B
poliovirus (Salk)
influenza
24
26. 26
Advantages of inactivated vaccines
Gives sufficient humoral immunity if boosters
given
• No mutation or reversio
Disadvantages of inactivated vaccines
• Many vaccinees do not raise immunity
• Boosters needed
• No local immunity (important)
• Higher cost
• Shortage of monkeys (polio)
• Failure in inactivation and immunization
with virulent virus
27. Vaccines from whole organisms
Many of the currently used vaccines to date
consist of inactivated or live but attenuated
bacterial cells or virus particles
Bacterial cells
Plague , pertusis, cholera
Inactivated
Tuberculosis
Attenuated BCG
Viral particals
Influenza , rubella virus Inactivated
Polio (Salk) Inactivated
Polio (Sabin) Attenuated
Yellow fever Attenuated
28. Toxoid Vaccines
Pathogenic toxin is
modified to
harmless toxoid
Examples of
Toxoid-based
vaccines include
tetanus and
diphtheria
28
29. Attenuated Vs Inactivated Vaccines
Attenuated Inactivated
Method of production:
Virulent strain grown under Virulence is inactivated
by adverse culture conditions chemical treatment or
by prolonged growth in
unnatural radiation
host or passage through
different unnatural hosts
Requirement of booster dose:
Generally single booster dose Multiple booster doses
is required are required
Stability:
Less stable More stable and
resistant
to natural temperature
30. Attenuated Vs Inactivated Vaccines
Type of host Immune responses:
Produce both cell mediated Mainly produces
and humoral immune response humoral response
Tendency to revert:
May revert to original virulent Does not revert to
virulent strain by recombination virulent form
with wild type strain or reverse
mutation
Attenuated Inactivated
31. Subunit Vaccines
• Risks associated with attenuated or
killed whole vaccines can be avoided by
subunit vaccines
• Consist of specific, purified
macromolecules derived pathogens
31
32. Subunit Vaccines
32
Protein subunit (toxoid)- diphteria, tetanus
Bacterial polysaccharide- S. pneumoniae, Nisseria
meningitidis
Viral glycoproteins- Herpes simplex virus glycoprotein D
Synthetic peptides produced from active epitopes of
antigen are used as vaccines.
Synthetic peptide vaccines for HIV, influenza, diphtheria
toxin, hepatitis B virus and malaria parasite are currently
being evaluated for their efficacy
Not very successful as peptides are not as immunogenic as
proteins
33. Subunit Vaccines
Recombinant pathogen proteins-
Gene coding any immunogenic protein cloned by
recombinant DNA technology
E.g. hepatitis Bs Ag gene cloned in yeast
35. Recombinant Vectors Vaccines
Attenuated viruses and bacteria serve as
vectors
Genes encoding major antigens of virulent
pathogens can be introduced into these
Wide range of organisms used as vectors:
vaccinia virus,
attenuated polio virus,
canary pox virus, adenovirus,
BCG strain of Mycobacterium bovis
36. The Hierarchy of Vaccines
First generation vaccines are whole-organism vaccines
– either live and weakened, or killed forms.
The so-called second generation vaccines are subunit
vaccines, consisting of defined protein antigens (such
as tetanus or diphtheria toxoid)
or recombinant protein components (such as the
hepatitis B surface antigen).
DNA vaccines are third generation vaccines
37. DNA Vaccines - The Third Generation
Vaccines
37
• 1796 Jenner: wild type animal-adapted virus
• 1800’s Pasteur: Attenuated virus
• 1996 DNA vaccines
38. DNA Vaccines
Made up of plasmid that has been genetically
engineered to produce one or two specific proteins
(antigens) from a pathogen.
The vaccine DNA is injected into the cells of the
body, where the "inner machinery" of the host cells
"reads" the DNA and converts it into pathogenic
proteins.
Because these proteins are recognised as foreign,
when they are processed by the host cells and
displayed on their surface, the immune system is
alerted, which then triggers a range of immune
39. Applications of DNA
Vaccines
DNA vaccines are in their early phase
of clinical trials.
There are no DNA vaccines in market
at present.
At present human trials are under way
for malaria, influenza, AIDS, Ebola and
Herpes.
40. Advantages of DNA Vaccines
40
Plasmids are easily manufactured in large amounts
DNA is very stable
DNA resists temperature extremes so storage and
transport are straight forward. Refrigeration is
not required
Stable for storage
Elicit both humoral & cell mediated immunity
Focused on Antigen of interest
Long term immunity
41. Disadvantages of DNA Vaccines
Limited to protein immunogen only
Extended immunostimulation leads to
chronic inflammation
Plasmid used is resistance to antibiotics for
selection. Can raise the resistance to same
antibiotic in the host
42. Conjugate Vaccines
Certain bacteria have
polysaccharide outer
coats that are poorly
immunogenic (T
independent Ags)
By linking these outer
coats to proteins (e.g.
toxiods), the immune
system can be led to
recognize the
polysaccharide as if it
were a protein antigen
Haemophilus influenzae
type B vaccine
42
43. Combination vaccines
43
DTP - Combination vaccine prevents three diseases
in one shot
Diphtheria, Tetanus (lockjaw), Pertussis (whooping
cough)
MMR
Measles, Mumps, Rubella
44. Edible vaccines
44
Antigens or antibodies expressed in plants
Oral administration
Cheaper
Exhibit good genetic stability
Do not require special storage conditions
Since syringes and needles are not used,
chances of infection are also less
46. Anti-idiotype vaccines
Idiotype- unique amino acid sequence of V
domain of a given Ab – Ag binding site as well
as antigenic determinant
Generation of an effective immune
response to a dangerous pathogen
without exposing the individual to any
form of pathogen as vaccine
It is known as anti-idiotype antibodies
Vaccines of this type have been developed
against pathogens of viral, bacterial or
parasitic type
51. Why aren't vaccines available for all
diseases ?51
The procedure for developing a vaccine is time taking and very
expensive
Vaccines are prioritized in following order:
Vaccines that fight diseases that cause the most deaths and
damage, like meningitis
Vaccines that prevent severe diseases like measles and influenza
Vaccines, like the one for rotavirus, that prevent significant
suffering
Companies must get significant return on investment
Some viruses mutate so quickly that traditional vaccines are
ineffective. A prime example is the HIV/AIDS virus
