detailed information

1. Vaccines
Muhammad Faisal Nadeem

2. What is a Vaccine?
 A vaccine is a non-pathogenic antigen that
mimics a particular pathogen in order to
elicit an immune response as if that actual
pathogen were in the body.
 The overall goal of a vaccine is to establish
immunity against that particular pathogen.

3. The Mechanism of a Vaccine
 In an ideal scenario, whenever
a vaccine is first administered,
it is phagocytized by an
antigen presenting cell (APC).
 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 (Th cells).

4.  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.
 Memory T-cells are also
established, however, they
usually have a shorter half-life
than memory B cells, thus,
they play only a minor role in
long-term immunity.
 Usually, there are no cytotoxic
T-cells formed whenever the
body responds to a vaccine.

5. Potential Shortcomings of Vaccines
 In some rare cases, a vaccine may
directly activate a B cell, without
stimulation from Th cells.
 Such antigens are known as T-
independent (TI) antigens.
 The problem with such a response
is that only Ig-M antibodies are
produced and there are no
memory cells established.
 Thus, such a vaccine will be
useless against establishing
immunity.

6.  Sometimes, the vaccine may be cleared from the body before it has
the chance to properly stimulate the immune system.
 Some pathogens, particularly viruses, has a tendency to mutate and
change there surface antigens, making a vaccine against them
ineffective.
 This is especially true of malaria, which is constantly changing its
surface antigens.
 Several different types of pathogens may cause similar infections,
thus, several different vaccines may be required for them.
 For example, Heamophilus influenzae, a bacterium, and influenzavirus,
a virus, causes diseases with similar symptoms.

7. The Importance of the 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.

8.  But in some cases, a pathogen may be so virulent that it
causes illness, even during the secondary immune response.
 In this situation, a vaccine may be ineffective.

9. 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.

10. 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.

11. 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.

12. Immune Stimulatory Complexes
 Consists of open cage-like
structures that contains
cholesterol and a mixture of
saponins.
 Allows delivery of the vaccine
to the cytosol, which
stimulates a response by
cytotoxic T-cells .
 Such an adjuvant may be
particularly useful in a vaccine
against cancer.

13. Routes of Administration
 There are three different routs
of administration:
 Intradermal administration.
 Three types are intravenous,
intramuscular, and
subcutaneous. DPT, MMR
 Oral administration.
 Vaccine is usually given in
liquid form.
 Foods, such as tomatoes,
have been engineered to
produce a vaccine. Polio
 Intranasal administration.
Influenza, Hepatitis B

15. 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.
 Boosters can also be given
during the primary response in
order to prolong and
strengthen the immune
response against the vaccine.
 Hep B Vaccine boosters

16. Types of Vaccines
 There are numerous types of vaccines.
 Each different type of has its own unique
properties.
 There function, however, is the same, to
establish immunity against a particular
pathogen.

17. Attenuated Virus/Bacteria
 These vaccines consist of live, but
weakened, viruses or bacteria.
 These organisms have been altered, either
genetically or chemically, in a way that
they are not pathogenic.
 An example is the attenuated virus vaccine
for yellow fever, which utilizes the YF17D
strain, a weakened form of the wild virus.

18. Killed Whole Organism
 This vaccine consist of
the actual pathogen,
however, it has been
killed, either by a heat
treatment or chemically.
 An example is the Salk
vaccine for polio, which
utilizes whole
polioviruses that have
been inactivated by
formaldehyde.

19. Toxoids
 Some species of bacterial
produce what is known as
exotoxins.
 Toxoids are vaccines which
consist of exotoxins that have
been inactivated, either by heat
or chemicals.
 These vaccines are intended to
build an immunity against the
toxins, but not necessarily the
bacteria that produce the
toxins.
.

20.  Preparation: most commercial preparations are
produced by the following steps:
1. Immunizing horses, Cows or sometimes human volunteers
2. Harvesting the serum
3. Purification and concentration of antitoxin
4. Sterilization of the antitoxin by filtration
5. Addition of chemical preservative
6. Standardization
 Examples
1. Diphtheria antitoxin
2. Tetanus antitoxin

21. Surface Molecules
 Proteins, carbohydrates, and lipids, that are found
on the surface of pathogens, are isolated and used
as a vaccine.
 Proteins are usually large and complex enough to
be used on there own.
 Carbohydrates and lipids requires conjugated
with a large protein in order to be immunogenic.
 An example of surface molecules used as a
vaccine are hepatitis B surface antigens.

22. Anti-Idiotype Vaccines
 In this unique type of vaccine, antibodies
from a sick individual are isolated.
 These antibodies are then injected into a
lab animal, which may then produce an
antibody whose antigen binding site
mimics the epitope that the original
antibody binds to.
 These antibodies are then isolated and
injected into a healthy individual, who
may produce antibodies with an antigen
binding site that binds to the antigen
binding site of the animals antibodies.
 Because the animals binding site
resembles the epitope of an antigen on a
particular pathogen, the individual will
have an immunity against that pathogen.

23. DNA Vaccines
 DNA vaccines consist of plasmids that contains genes for certain types
of antigens.
 Once administered, the plasmid is taken up by the target cell and the
genes are expressed.
 The cell then either excretes the antigen or displays it on an MHC-I
molecule.

24. Chimeric Vaccines
 Chimeric vaccines usually consist of attenuated viruses
that have been engineered to carry antigens from multiple
types of pathogens.
 For example, the yellow fever vaccine YF17D has been
engineered to carry antigens from HIV, different types of
bacteria, malaria, even cancer.
 The aim of a chimeric vaccine is the establishment of
immunity against several different diseases with one
administration.

25. Vaccine Production Methods
 There are three main vaccine manufacturing
strategies:
 In-vivo
 In-vitro
 Chemical Synthesis
 Some vaccines can be produced using any
one of the three methods while for other
vaccines, only one method will work.

26. In-Vivo
 In in-vivo manufacturing, the
vaccine is produced inside a
living organism.
 Embryonated Chicken eggs
are are commonly used,
particularly in producing flu
vaccines.
 Vaccines, such as anti-
idiotype, can also be produced
in lab animals, such as mice.
 There are even some species
of plant, such as bananas, that
have been genetically
engineered to produce a
vaccine.

27. In-Vitro
 Here, using recombinant DNA
technology, vaccines can be
produced in yeast cultures,
bacterial cultures, or cell
cultures.
 Recombinant vaccines, such as
chimeric vaccines, are
produced in this manor.
 Attenuated virus/bacteria
vaccines can also be produced
this way.

28. Chemical Synthesis
 Here, instead of using
biological systems to
produce a vaccine, a vaccine
can be produced in a lab.
 Vaccines that utilize
synthetic peptides as well as
conjugated lipids and
polysaccharides are
manufactured this way.
 Usually, this method is used
in combination with either
in-vivo or in-vitro
production.

29. Risks Associated With Vaccines
 The primary risk associated with vaccines, especially vaccines that
utilize live organisms, is that the vaccine itself causes illness.
 This Happened with the orally administered Sabin vaccine for
polio, where some individuals became ill and, in rare cases,
even spread the illness to other individuals who were not
exposed to the vaccine.
 Another risk is that the vaccine may behave as a super antigen and
over stimulate the immune system.
 Yet a third risk is that some individuals may have an allergic reaction
to the vaccine, especially vaccines produced in embrionated chicken
eggs and in transgenic plants.

30. Specific Antigens: Viruses and Bacteria
 Almost every type of
viral and bacterial
pathogen has a vaccine,
or, there is one under
development for it.
 This is because Vaccines
use viral or bacterial
components which
causes the immune
system to react as if an
actual virus or
bacterium has invaded
the body.

31. Parasites Currently the only
vaccines being developed
for parasites are vaccines
for protozoa, particularly
the protozoan
Plasmodium, the causative
agent of malaria.
 Because of its complex
life-cycle and its tendency
to regularly change its
surface antigens, the
development of a malaria
vaccine has been difficult
to achieve.

32. Cancer
 Any type of vaccine against
cancer must be able to elicit a
response by cytotoxic T-cells,
which is something
conventional vaccines do not
do.
 In order for a vaccine to do
this, it has to be taken up by
the cancer cell and the
vaccine’s antigens be displayed
on the cell’s MHC-I molecules.
 In this case, the cancer must be
present before the vaccine can
be administered.
 So, does this really make it a
vaccine?

33. Nicotine
 Perhaps the most unusual “pathogen” that a
vaccine is being developed for is nicotine
 A vaccine consisting of nicotine, which is a hapten,
conjugated to a larger carrier molecule.
 When administered, the body will actually mount
an immune response and produce antibodies
against nicotine.
 The problem with this vaccine is that nicotine by
itself will not cause an immune response, even if
memory cells against it exist.
 Thus, the “vaccine” must be administered, in
large doses, along with administration of nicotine.

35. Type 1 hypersensitivity
= immediate hypersensitivity
= Ig E mediated hypersensitivity
Etiology
General view:
 On primary exposure to an allergen , specific IgE
is produced and fixed to mast cells and basophils
 On further exposure to same allergen , the
allergen cross links the cell bound IgE molecules
→ release of several active mediators
B) Gamma Globulins
 Preparation:
Prepared from pooled healthy adult human plasma or serum by
cooled ethanol fractionation
 Uses
The Preparation contains a variety of different antibodies
(mainly IgG) against several micro-organisms, so used for:
 Passive immunization of case contacts against various diseases e.g.
measles
 Maintenance of immuno defieceint patients.
C) Specific immunoGlobulins
 Preparation:
this is Gamma globulins prepared from :
1. Plasma of patients recovered from an specific disease
2. Hyper-immunized human volunteers.
 Examples:
immunoglobulin of Hepatitis B, Rabies, tetanus and Anti-D

36. Similarities between vaccines and
other drugs
 Vaccines are also medicines
 Potential for adverse effects
 Multiple ingredients
 Potential for interaction with disease and
other medicines
 Also need to comply with standards of
safety, efficacy and quality

37. The Principles of Immunization
 • To prime recipient’s immune response
 • To generate B and T memory cells
 • To heighten immune response (humoral and
 cell mediated) to pathogens
 • Vaccine(s) should
 – have minimal adverse effects
 – prevent/reduce severity of infectious diseases
 (effectiveness)
 – be of assured quality and available for general use

38. The ideal vaccine
 • Immunogenic
 • Long lasting immunity
 • Safe
 • Stable in field conditions
 • Combined
 • Single dose
 • Affordable (and accessible) to all

39. VACCINE REACTIONS
Common, minor reactions
 – Part of immune response to vaccine,
 Settle on their own
 – Warn parents and advise how to manage
 – e.g. fever, malaise etc.
Rare, more severe reactions
 – Usually require clinical management, e.g.,
 severe allergic reaction (such as
 anaphylaxis), Vaccine specific reactions
 (e.g. BCG osteitis)

44. EPI (Expanded Program of
Immunization) Pakistan
AIM:
EPI Pakistan targets with
vaccination 5.8
million children
against 8 diseases
(childhood
tuberculosis,
poliomyelitis,
diphtheria, pertussis,
tetanus, hepatitis-B,
haemophilus
influenzae type-b and
measles

46. EPI SCHEDULE:
ROUTINE IMMUNIZATION SCHEDULE:
 BCG & OVP 0 dose are given at birth,
 DPT1 (Diphtheria, Pertussis, Tetanus), HBV1
(Hepatitis B Virus) & Polio1 at 6
 DPT2, HBV2 & Polio2 at 10 and
 DPT3, HBV3 & Polio3 14 weeks
 Measles vaccine at the age of 9 months.
 The pregnant ladies and child bearing age ladies
are provided immunization against TT (tetanus
toxin).

47. EPI schedule continues…
THE SCHEDULE OF VACCINATION OF
PREGNANT WOMEN AND LADIES OF
CHILD BEARING AGE IS:
 TT 1 at first contact,
 TT 2 at least 4 weeks after 1st dose,
 TT 3 at least 6 months after 2nd dose,
 TT 4 at least 1 year after 3rd dose and
 TT 5 at least one year after 4th dose)