IMMUNOTHERAPY

By:
Dr: Mohamed Abdelrahman

1
 Immunotherapy is the process involving the
use of immunological product for prevention,
control or treatment of infectious diseases,
caused by pathogenic microorganisms or its
toxin.

2
 Introduction

 Immunological Products comprise a group of

pharmaceutical preparations with diverse origins
but with a common pharmacological purpose: the
enhancement of a recipient’s immune status in a
manner that provides immunity to infectious
disease. The immunological products that are
generally available today are of three types:
Immunosera, Human Immunoglobulins, and
Vaccines.

3
 Immunosera, is ready-made antibodies
derived from animal which was vaccinated to
produce antibodies which will be used to fight
against the those antigens.
 Immunosera was very widely used in the
prophylaxis and treatment of many infections,
are little used today, as vaccines have made
some immuno-sera unnecessary and lack of
proven therapeutic benefit has caused others to
be relegated to immunological history.

4
 Tetanus antitoxin is an exception in that it is
a very effective prophylactic that is still used
in countries where there are inadequate
supplies of tetanus Human immunoglobulin.
 Immunoglobulins which derived from human
have important but limited uses.

5
 Vaccine is antigen which stimulate the immune
system to produce an immune response either in
form of antibody or cell mediated immunity.
 Its the most important immunological products.
They induce immunity to many diseases, and in so
doing they have provided benefits for humankind
and for its animals, comparable with the benefits
provided by anaesthetics and antibiotics.

6
 Smallpox vaccine, continuously distributed under
the aegis of the WHO, has made possible the
eradication of one of the world’s most terrible
infections.
 Diphtheria, tetanus, whooping-cough,
poliomyelitis, measles, and German measles
vaccines have been quite effective in those
countries in which there have been the resources
and they will to deploy them in health care
programmes. Vaccines that provide protection
against many other infections are available for use
in appropriate circumstances. 7
 Vaccines achieve their protective effects by
stimulating a recipient’s immune system to
synthesise antibodies that promote the destruction
of infecting microbes or neutralize bacterial
toxins. This form of protection, known as active
immunity, develops in the course of days, and in
the cases of many vaccines develops adequately
only after two or three doses of vaccine have been
given at intervals of days or weeks. Once
established, this immunity lasts for years but it
may need to be reinforced by ‘booster’ doses of
vaccine given at relatively long intervals.
8
 Immunosera and human immunoglobulins
depend for their protective effects on their
content of antibodies derived, in the case of
Immunosera, from immunized animals and, in
the case of immunoglobulins, from humans
who have been immunized or who have high
antibody titres consequent upon prior
infection.

9
 This form of immunity, known as passive immunity,
is achieved immediately but is limited in its duration
to the time that protective levels of antibodies remain
in the circulation.
 A feature that is common to vaccines, Immunosera
and human immunoglobulins is the marked
specificity of their actions. Each provides immunity
to only one infection. This specificity has led to the
development of vaccines and Immunosera with
several different components such as are present in
the widely used diphtheria/tetanus/pertussis vaccines
that are used to prevent the infectious diseases that
commonly afflict infants and young children.
10
 Vaccines
 The vaccines currently used for the prevention
of the infectious diseases of humans all
originate, albeit in a variety of ways, from
pathogenic microbes. The essence of vaccine
manufacture thus consists of procedures which
produce from dangerous pathogens, their
components or their products, the immunogens
that are devoid of pathogenic properties but
which, nonetheless, retain the property of
inducing a protective response in those to whom
they are administered. 11
 The methods that are used by vaccine
manufacturers are constrained by costs, by
problems of delivery to the vaccines and, most
of all, by the biological properties of the
pathogens from which vaccines are derived.
Even so, the vaccines used in conventional
vaccination programmes today are of only
nine readily recognizable types.

12
 Live Vaccines -1
 Live vaccines are preparations of live bacteria or
viruses which, when administered in an appropriate
way, cause symptomless or almost symptomless
infections. In the course of such an infection the
constituents of the microbes in a vaccine evoke an
immune response which provides protection against a
serious natural disease. Live vaccines have a long
history. The very first vaccine, smallpox vaccine, was
a live vaccine. It was introduced in 1796 by Edward
Jenner, who recognized that an attack of the mild
condition known as cowpox protected milkmaids from
smallpox during epidemics of this dreaded disease.
13
 The process involved taking some fluid, the lymph,
from a cowpox pustule on the hand of a milkmaid
and used it to inoculate a small boy. A little later, the
boy was inoculated with the lymph from a case of
smallpox, with nothing happening. The boy,
protected as he was by the cowpox infection,
remained well. Jenner’s use of the causative
organism of one disease to provide protection against
another is paralleled by the use of bacille Calmette-
Guerin (BCG) strain of bovine tubercle bacilli to
protect against infections with the human strains.

14
 However, in this case, there is the difference that
the ability of the BCG strain to cause disease, its
pathogenicity or virulence, has been reduced by
many sequential sub-cultivations on laboratory
media. Live vaccines such as smallpox and BCG
vaccines that rely on the phenomenon of ‘cross-
protection’ are exceptions to the generality that
most vaccines are derived from the causative
organisms of the diseases against which each is
intended to provide protection.

15
 Likewise, polioviruses from human infections
were grown in the laboratory in such a way
that it was possible to select infectious but
innocuous progeny viruses suitable for use in
live (oral) poliovaccines. Comparable
procedures have been used to obtain the
viruses that are currently used in live measles,
mumps rubella and yellow fever vaccines. The
microbes with the reduced ability to cause
disease that are used in live vaccines are said
to have attenuated virulence and are often
referred to as attenuated or vaccine strains.
16
Killed Vaccines -2

 Killed vaccines are suspensions of bacteria or

of viruses that have been killed by heat or by
disinfectants such as phenol or formaldehyde.
Killed microbes do not replicate and cause an
infection but keeps it intact so that the
immune system can still recognise it. Because
killed vaccines can’t replicate, they tend to
provide shorter length of protection than live
vaccines, and more likely to require booster
dose to create long term immunity.
17
Toxoid (inactivated toxin) -3

 Some bacterial diseases are not directly caused

by bacterium itself but by toxin produced by
bacterium, such as tetanus and diphtheria.
 Immunization for this type of pathogen can be
made by inactivating the toxin that causes
disease symptoms. This can be done via
treatment with chemical such as formalin, or
by using heat or other methods. Immunization
created using inactivated toxin are called
toxoid, such as tetanus and diphtheria toxoid
18
Subunit Vaccines -4

 Subunit vaccines contain only pieces of

pathogens they protect against.
 Subunit vaccines used only part of a target
pathogen to provoke a response from the
immune system. This may be done by isolating
a specific protein from a pathogen and
presenting it as an antigen on its own. The
acellular pertussis vaccine and influenza
vaccine are examples of subunit vaccine.
19
Conjugate vaccine -5

 Conjugate vaccine made using a combination

of two different components, such as pieces
from the coat of bacteria, these coat are
chemically linked to a carrier protein, and the
combination is used as vaccine.
 Many bacteria molecules are coated by a sugar
called polysaccharide. This coating hides or
masks the germ (antigens) so that the
immature immune systems of infants are not
able to recognize it.
20
 Polysaccharide attached to a stronger protein,
when the immune system responds to the
protein, it also responds to the polysaccharide.
 Examples include Haemophilus Influenza
conjugate vaccine (Hib) and Pneumoccocal
conjugate vaccine.

21
DNA vaccines -6

 A recent development, associated with

research into gene therapy, has been the use of
DNA encoding specific virulence factors of
defined pathogens to evoke an immune
response. The DNA is introduced directly into
tissue cells by means of a transdermal gene-
gun and is transcribed by the recipient cells.
 Accordingly the host responds to the antigenic
material produced as though it were an
infection.
22
 The course of release of the antigen reflects
that of a natural infection and, therefore, a
highly specific response is invoked.
Eventually the introduced DNA is lost from
the recipient cells and antigen release ceases.
 the hepatitis B vaccine currently used in US is
a recombinant vaccine.

23
RNA vaccines -7

 RNA vaccines use mRNA (messenger RNA)

inside a lipid (fat) membrane. This fatty cover
both protects the mRNA when it first enters
the body, and also helps it to get inside cells
by fusing with the cell membrane. Once the
mRNA is inside the cell, machinery inside the
cell translates it into the antigen protein. This
mRNA typically lasts a few days, but in that
time sufficient antigen is made to stimulate an
immune response.
24
 It is then naturally broken down and removed
by the body. RNA vaccines are not capable of
combining with the human genetic code
(DNA).
 Pfizer BioNTech and the Moderna COVID-19
vaccines are both RNA vaccines.

25
Viral Vectored Vaccines-8

 As with nucleic acid vaccines, viral vectored

vaccines are a newer technology, using
harmless viruses to deliver the genetic code of
target vaccine antigens to cells of the body, so
that they can produce protein antigens to
stimulate an immune response.
 AstraZeneca COVID-19 vaccine is viral
vectored vaccine.

26
27
Synthetic peptide vaccine-9

 Also called epitope based vaccine, its principle is to

identify the peptide sequences that trigger a protective
immune response and to use completely synthetic
versions of these as the vaccine substance. Because they
would be synthetic, there would be no risk of mutation
or reversion, little or no risk of contamination by
pathogenic or toxic substances, and chemical
manipulation of the peptide structure could possibly
increase stability and decrease unwanted side effects
seen in the native sequence.
 Malaria, HCV and HIV are currently under development
synthetic peptide vaccine.
28
Adjuvants

 An adjuvant is an ingredient used in some

vaccines that helps create a stronger immune
response in people receiving the vaccine. In other
words, adjuvants help vaccines work better. Some
vaccines that are made from weakened or killed
germs contain naturally occurring adjuvants and
help the body produce a strong protective immune
response. However, most vaccines developed
today include just small components of germs,
such as their proteins, rather than the entire virus
or bacteria.
29
 Adjuvants help the body to produce an
immune response strong enough to protect the
person from the disease he or she is being
vaccinated against. Adjuvanted vaccines can
cause more local reactions (such as redness,
swelling, and pain at the injection site) and
more systemic reactions (such as fever, chills
and body aches) than non-adjuvanted
vaccines.
 Example of adjuvant is Aluminum hydroxide.
30
 Tetanus Toxoid (TT) Vaccine ]1
 What is TT vaccine?
 Tetanus toxoid (TT) vaccine protects against tetanus.
It is provided as a liquid in vials and also in prefilled
auto-disable injection devices.
 It is available in a number of different formulations:
 TT vaccine protects only against tetanus and
neonatal tetanus.
 DTP, or diphtheria-tetanus-pertussis vaccine, protects
against diphtheria, tetanus, and pertussis.
 DT, or diphtheria-tetanus toxoids vaccine, protects
against diphtheria and tetanus.
31
 Because it contains high levels of diphtheria
toxoid, it should not be given to children older
than six years old or adults.
 Td, or tetanus-diphtheria toxoids adult dose
vaccine, is the same vaccine as DT, but with a
lower diphtheria toxoid dose.
 It is suitable for children older than six years
old and adults, including pregnant women.

32
 Td has the added advantage of protecting against
diphtheria and tetanus.
 When given to women of childbearing age,
vaccines that contain tetanus toxoid (TT or Td) not
only protect women against tetanus, but also
prevent neonatal tetanus in their newborn infants.
 When TT or Td vaccine is given to a woman who is
or who becomes pregnant, the antibodies that form
in her body are passed to her foetus.
 These antibodies protect the baby against tetanus
during birth and for a few months afterwards. They
also protect the woman against tetanus.
33
 A three-dose course of TT or Td provides protection
against maternal and neonatal tetanus for at least five
years. A maximum of five doses will protect women
throughout their childbearing years.
 When vaccines containing tetanus toxoid stand for a
long time, the vaccine separates from the liquid and
looks like fine sand at the bottom of the vial. Shake the
vial to mix the vaccine and liquid again before giving
the vaccine.
 TT/DT/Td/DTP vaccines should never be frozen. The
“shake test” will determine if the vaccine has been
damaged by freezing. If the vaccine fails the shake test
you must discard it.
34
 How safe are TT, Td, and DT
vaccines and
 What are their potential side-effects?
 Vaccines containing tetanus toxoid cause very few serious
reactions but quite frequent mild reactions.
 Mild reactions to TT, Td, and DT vaccines include:
 Soreness. About one in ten people who receive the
vaccines have mild pain, redness, warmth, and swelling at
the injection site for about one to three days after the
injection. This mild reaction is likely to be more common
after later doses than earlier ones, and may affect between
50% and 85% of people who receive booster doses.
 Fever. About one in ten people may develop a mild fever
after receiving the vaccines. 35
 Tetanus toxoid immunization schedule for routine
immunization of pregnant women; Dose of TT or
Td; When to give; Expected duration of protection
 1 At first contact or as early as possible in pregnancy;
none
 2 At least 4 weeks after TT 1 protects from1–3 years
 3 At least 6 months after TT 2 or during subsequent
pregnancy At least 5 years
 4 At least 1 year after TT 3 or during subsequent
pregnancy At least 10 years
 5 At least 1 year after TT 4 or during subsequent
pregnancy; for all childbearing years and possibly
longer
36
 As the women reach childbearing age the
incidence of maternal and neonatal tetanus is
expected to decline further: three properly spaced
doses of DTP given in childhood are considered
equivalent in protection to two doses of TT/Td
given in adulthood.
 a Recent studies suggest that the duration of
protection may be longer than indicated in the
table. This matter is currently under review.

37
 Administration summary: TT vaccine
 Type of vaccine: Toxoid as DT, TT or Td
 Number of doses: At least two primary doses
 Schedule: See previous table
 Booster: TT/Td every 10 years or during pregnancy. DT
18 months to six years of age
 Contraindications: Anaphylactic reaction to previous
dose
 Adverse reactions: Mild local or systemic reactions are
common and increase in frequency with increasing
numbers of doses, and may constitute a contraindication
to further doses
 Special precautions: Reduced diphtheria (Td instead of
38
 Dosage: 0.5ml
 Injection site: Outer upper arm
 Injection type: Intramuscular
 Storage: Store between 2°C–8°C. Never freeze
 WHO recommends that, where resources
permit, an additional dose of DTP be given
approximately one year after completion of the
primary doses. However, the need for and
timing of additional booster doses of DTP, DT
or Td should be addressed by individual
national programmes.
39
Diphtheria-Tetanus-Pertussis (DTP) Vaccine ]2
 What is DTP vaccine?
 Diphtheria-tetanus-pertussis vaccine is made from
diphtheria toxoid, tetanus toxoid, and pertussis vaccine.
It is a liquid vaccine. If a vial of DTP vaccine stands for
a long time, fine particles may separate from the liquid.
They look like fine sand at the bottom of the vial.
Before giving the vaccine shake the vial to mix the
vaccine and liquid.
 DTP vaccine should never be frozen. The “shake test”
will determine if the vaccine has been damaged by
freezing. If the vaccine fails the shake test you must
discard it.
40
 How safe is DTP vaccine and
?what are its potential side-effects
 Usually, reactions to DTP vaccine are mild. The side-effects
include:
 Fever. Up to half of the children who receive DTP vaccine may
have a fever in the evening after receiving the injection. The
fever should disappear within a day. Note that a fever that
begins more than 24 hours after a DTP injection is not likely to
be a reaction to the vaccine.
 Administering paracetamol or any appropriate antipyretic at the
time and at four and eight hours after immunization decreases
the subsequent incidence of febrile and local reactions.
 Soreness. Up to half of the children may have pain, redness, or
swelling at the injection site.
41
 Crying for more than three hours, mostly
because of pain, can be observed in up to 1%
of infants.
 More severe reactions reported include
convulsions (usually related to fever, one case
in 12 500 doses administered) and hypotonic–
hyporesponsive episodes (one case in 1750
doses administered). Anaphylactic reactions
are extremely rare.
 There is no evidence that the vaccine causes
any serious neurological disorder such as
encephalopathy. 42
 Administration summary: DTP Vaccine

 Type of vaccine: Diphtheria and Tetanus as toxoids. Pertussis

as killed whole-cell bacterium
 Number of doses: At least three primary doses
 Schedule: 6, 10, 14 weeks of age (a)
 Booster: 18 months to 6 years of age (b)
 Contraindications: Anaphylactic reaction to previous dose or to
any constituent
 Adverse reactions: Mild local or systemic reactions are
common
 Special precautions: DTP not usually given over 6 years of age
 Dosage: 0.5 ml
43
 Injection site: Outer mid-thigh in infants/outer upper
arm if older
 Injection type: Intramuscular
 Storage: Store between 2° C – 8° C. DTP vaccine
should never be frozen
 a) There is considerable variation in the timing of the
three primary doses between different national
immunization schedules.
 b) WHO recommends that, where resources permit, an
additional dose of DTP be given after completion of the
primary doses. However, the need for and timing of
additional booster doses of DTP should be addressed by
individual national programmes.
44
 Hepatitis B (Hep B) vaccine ]3
 What is Hep B vaccine?
 Hepatitis B (Hep B) vaccine is a cloudy liquid that
is provided in single- or multi-dose vials or in
prefilled auto-disable (AD) injection devices.
 Because the Hep B vaccine contains only one
antigen, it is called a monovalent vaccine. Hep B
vaccine is also available in combination DTP - Hep
B and DTP-Hep B + Hib vaccines. Only
monovalent Hep B vaccine should be used as a birth
dose, the dose given within the first week of life.
Combination vaccines should not be used at birth,
45
 If Hep B vaccine stands for a long time, the
vaccine may separate from the liquid. When
separated, the vaccine looks like fine sand at
the bottom of the vial. Shake the vial to mix
the vaccine and liquid before using the
vaccine. HepB vaccine should never be frozen.
 The “shake test” will determine if the vaccine
has been damaged by freezing. If the vaccine
fails the shake test you must discard it.
46
 How safe is Hep B vaccine and what
?are its potential side-effects
 Hep B vaccine is one of the safest vaccines.
 Mild reactions include:
 Soreness. About 15% of adults and 5% of children have
tenderness, redness, or mild swelling at injection site.
 Fever. About 1% to 6% of those who receive the
vaccine develop a mild fever that lasts one or two days
after injection of the vaccine. Reactions and
complications due to the vaccine are rare.
 Allergic reactions, such as rash, difficulty in breathing,
and choking, occur about once every 600 000 doses. No
fatal allergic reaction has been reported. 47
Administration summary: Hep B vaccine
 Type of vaccine: Recombinant DNA or plasma-derived
 Number of doses: Three doses
 Schedule: Several options (see above)
 Booster: None
 Contraindications: Anaphylactic reaction to a previous dose
 Adverse reactions: Local soreness and redness, rarely anaphylactic
reaction
 Special precautions: Birth dose must be given if there is a risk of
perinatal transmission
 Dosage: 0.5ml
 Injection site: Outer mid-thigh (infants)/outer upper arm (children
and adults)
 Injection type: Intramuscular
48

DTP – Hep B combination vaccine ]4

 What is DTP-Hep B vaccine?

 DTP-Hep B is a quadrivalent (or tetravalent)
vaccine that protects against four diseases:
diphtheria, tetanus, pertussis, and hepatitis B.
DTP-Hep B is a liquid that comes in single- or
multi-dose vials.
 The vaccine can separate from the liquid if it
stands for a long time. Shake the vial to mix the
vaccine and liquid before using it. DTP-Hep B
vaccine should never be frozen.
49
 The “shake test” (see Module 3) will
determine if the vaccine has been damaged by
freezing. If the vaccine fails the shake test you
must discard it.
 Because the DTP vaccine should not be given
to infants younger than six weeks old, DTP-
Hep B vaccine should not be as a birth dose.
DTP-Hep B is used for subsequent vaccine
doses.
50
 How safe is DTP-Hep B vaccine and what are its
potential side-effects?
 Mild reactions to the vaccine include:
 Soreness. Some infants may develop mild soreness,
redness, or swelling at the injection site, but this will
usually go away within one to three days.
 Fever. As with DTP vaccine, some infants may
develop a mild fever.
 Serious reactions to the DTP-Hep B vaccine occur at
a frequency similar to the DTP vaccine and the Hep B
vaccine (see Sections 1 and 7 of this module). 51
Administration summary: DTP-Hep B
combination vaccine
 Type of vaccine: Quadrivalent or tetravalent vaccine
 Number of doses: Three
 Schedule: 6, 10, 14 weeks of age
 Booster: Not recommended
 Contraindications: Anaphylactic reaction to previous dose
 Adverse reactions: Mild local or systemic reactions are
common
 Special precautions: Do not use as a birth dose; Usually not
given over 6 years of age
 Dosage: 0.5ml
 Injection site: Outer mid-thigh
 Injection type: Intramuscular
52
Haemophilus influenzae type b (Hib) Vaccine ]5

 What is Haemophilus influenzae type b vaccine?

 Haemophilus influenzae type b vaccine prevents
meningitis, pneumonia, epiglottitis, and other serious
infections caused by Haemophilus influenzae type b
bacteria. The vaccine will not protect against these
conditions if they are caused by other agents.
 Hib vaccine is available in two forms, liquid or freeze-
dried. Each is available as monovalent vaccine or in
combination with other vaccines. Many countries give
Hib combined with DTP and Hep B vaccines (DTP-
Hep B + Hib) (see Section 10 of this module).
53
 How safe is Hib vaccine and what are its
potential side-effects?
 Haemophilus influenzae type b vaccine is very
safe. There are no known serious reactions to the
vaccine.
 Mild reactions include:
 Soreness. About 5% to 15% of those who receive
Hib vaccine develop redness, swelling, or mild
pain at the site of the injection.
 Fever. A short time after immunization, between
2% and 10% of people may develop a mild fever.

54
 Administration summary: Hib vaccine
 Type of vaccine: Conjugate
 Number of doses: two or three doses (depending on
manufacturer)
 Schedule: 6, 10, 14 weeks of age for three doses schedule
(depending on manufacturer)
 Booster: None
 Contraindications: Hypersensitivity to previous dose
 Adverse reactions: Mild local reaction
 Special precautions: None
 Dosage: 0.5ml
 Injection site: Outer mid-thigh for infants. Outer upper arm for
older children
 Injection type: Intramuscular
55

 DTP-Hep B + Hib Combination Vaccine ]6

 What is DTP-Hep B+Hib vaccine?

 DTP-Hep B+Hib vaccine is called a pentavalent
vaccine because it protects against five diseases:
diphtheria, tetanus, pertussis, hepatitis B, and
Haemophilus influenzae type b.
 Do not use DTP-Hep B+Hib as a birth dose.
You may use the vaccine for subsequent doses.

56
 DTP-Hep B+Hib vaccine must be
reconstituted before use. The freeze-dried Hib
component is reconstituted with the liquid
DTP-Hep B component.
 The vaccine comes in two-dose vials.
Reconstituted DTP-Hep B+Hib vaccine must
be discarded after six hours or at the end of the
immunization session, whichever comes first.

57
 How safe is DTP-Hep B + Hib vaccine? And what are its
potential side-effects?
 The number of cases of serious reactions to the DTP-Hep B+
Hib vaccine are similar to those of the other vaccines that
contain DTP.
 If a serious reaction does occur, health workers should report
the problem to supervisors immediately.
 Children who have a severe reaction should not receive
additional doses of vaccine.
 Mild reactions to the vaccine include:
 Soreness. Some children may develop mild soreness, redness,
or swelling at the injection site, but this will usually go away
within one to three days.
 Fever. As with DTP vaccine, some children may develop a
mild fever.
58
 Administration summary: DTP-Hep B + Hib
combination vaccine
 Type of vaccine: Pentavalent vaccine
 Number of doses: Three
 Schedule: 6, 10, 14 weeks of age
 Booster: None
 Contraindications: Do not use as a birth dose
 Adverse reactions: Mild local and systemic reactions are
common
 Special precautions: Do not use as a birth dose, usually not
given over 6 years of age
 Dosage: 0.5 ml
 Injection site: Outer mid-thigh
 Injection type: Intramuscular
59
Measles Vaccine ]7

 What is measles vaccine?

 Measles vaccine is provided as a powder, with
a diluent in a separate vial. Before it can be
used, it must be reconstituted. It is essential
that only the diluent supplied with the vaccine
be used. After reconstitution measles vaccine
should be kept at 2°C–8°C. Any remaining
reconstituted vaccine must be discarded after
six hours or at the end of the immunization
session, whichever comes first.
60
 In countries where vitamin A deficiency is
common, vitamin A supplements are often given
at the same time as the vaccine.
 In addition, some countries include vaccine for
rubella with measles vaccine (MR), or use a
combination measles-mumps-rubella (MMR)
vaccine.

61
 How safe is measles vaccine and
? what are its potential side-effects
 Mild reactions to the vaccine are not uncommon. These
include:
 Soreness. Some children may experience pain and
tenderness at the injection site within 24 hours of
immunization. In most cases, these reactions will resolve
within two or three days without any medical attention.
 Fever. About 5% of children develop a moderate fever
five to 12 days after receiving the vaccine. It usually
lasts a day or two.
 Rash. About one in 20 children develop a mild rash up
to 12 days after receiving the vaccine. The rash usually
62
 Severe reactions to measles vaccine are rare;
anaphylaxis has been estimated to occur about
once for every million doses administered,
while a severe allergic reaction can occur once
for every 100 000 doses and one case of
thrombocytopenia for every 30 000 doses.
Encephalitis has been reported to occur in no
more than one per million doses administered
and, even in such cases, there is no definite
proof that the vaccine was the cause.

63
 What is the “second opportunity”
? for measles immunization

 All children should have a second opportunity to

receive measles vaccine. This increases the
proportion of children who receive at least one
dose and helps to assure measles immunity in
previously vaccinated children who failed to
develop such immunity.
 This opportunity may be delivered either through
routine immunization services or through periodic
mass campaigns.
64
Administration summary: Measles Vaccine

 Type of vaccine: Live attenuated viral

 Number of doses: One dose. Second opportunity not
less than one month after first dose
 Schedule: At 9–11 months of age in countries where
measles is highly endemic a, later in countries with
high levels of control or low mortality
 Booster: A second opportunity for measles
immunization is recommended (routine or campaign)
 Contraindications: Severe reaction to previous dose;
pregnancy; congenital or acquired immune disorders
(not HIV infection) 65
 Adverse reactions: Malaise, fever, rash 5–12 days later;
idiopathic thrombocytopenic purpurea; rarely, encephalitis,
anaphylaxis
 Special precautions: None
 Dosage: 0.5ml
 Injection site: Outer mid-thigh/upper arm depending on the
age
 Injection type: Subcutaneous
 Storage: Store between 2°C–8°C (vaccine maybe frozen for
long-term storage but not the diluent)
 a) Infants at high risk (HIV-infected, in closed communities
such as refugee camps, or in the presence of an outbreak)
may receive a dose at 6 months of age followed by an extra
dose at 9 months.
66
Measles-Rubella (MR) and Measles-Mumps ]8
Rubella (MMR) Combination Vaccines
 What are the MR and MMR vaccines?
 Some countries use combination vaccines for measles
and rubella (MR) or for measles, mumps, and rubella
(MMR). MR and MMR vaccines are provided in
powder form with diluents and must be reconstituted
before they can be used. It is essential that only the
diluent supplied with the vaccine be used. MR and
MMR vaccines should be kept at 2‫؛‬C–8°C after
reconstitution. Any remaining reconstituted vaccine
must be discarded after six hours or at the end of the
immunization session, whichever comes first.
 67
How safe are the MR and MMR vaccines
and
 What are their potential side-effects?
 Mild reactions to the vaccines include:
 Fever. As with the single-antigen measles
vaccine, about 5% to 15% of children develop
a mild fever within five to 12 days of
receiving the vaccine.
 Rash. Again as with the measles vaccine,
about one in 20 children develop a mild rash
about five to 12 days after being immunized.
68
 Severe reactions are rare and similar to that
experienced after receipt of the measles
vaccine. Although an association between
MMR and autism has been suggested, there is
absolutely no evidence of such an association.
 In addition, rubella-containing vaccines may
result in a temporary form of arthritis from one
to three weeks after vaccination in up to one in
four post-pubertal females. These reactions are
very rare in young children

69
 Mumps-containing vaccines may result in rare
cases of parotitis and some cases of aseptic
meningitis. Children recover without sequelae
although some may need to be hospitalized.
The risk of developing this complication
varies depending on the vaccine strain used.

70
 Administration summary:
MR and MMR vaccines
 Type of vaccine: Live attenuated viral
 Number of doses: One dose
 Schedule: Generally 12–15 months
 Booster: A second opportunity for immunization is
recommended (routine or campaign)
 Contraindications: Severe reaction to previous dose;
pregnancy; congenital or acquired immune disorders
(not HIV infection). Although it is not recommended to
administer the vaccine during pregnancy, there has never
been any evidence of damage to the foetus from
vaccinating the mother during pregnancy. 71
 Adverse reactions: Same as measles vaccine,
plus cases of arthritis in adolescent females for
rubella containing vaccine and parotitis; rarely
aseptic meningitis with mumps-containing
vaccines may occur
 Special precautions: None
 Dosage: 0.5ml
 Injection site: Outer mid-thigh/upper arm
depending on the age
 Injection type: Subcutaneous
 Storage: Store between 2°C–8°C (vaccine maybe
frozen for long-term storage but not the diluent).
72
Oral Polio Vaccine (OPV) Sabin ]9

 What is OPV?
 Oral polio vaccine (OPV) protects against the virus
that causes polio. It is a liquid vaccine that is
provided in two types of containers:
 1. Small plastic dropper bottles
 2. Glass vials with droppers in a separate plastic bag.
 WHO does not – as of July 2003 – recommend the
adoption of IPV (Salk), either alone or in a
sequential schedule, in developing countries for the
following reasons:
73
 The unresolved issues related to the
immunogenicity of IPV when administered at
birth, six, ten and 14 weeks of age.
 The relatively high cost of IPV, and
 The operational complexities of introducing a
vaccine which requires syringes and needles,
while OPV is given orally.
 Storage condition OPV can be stored at room
temperature

74
 How safe is OPV and
what are its potential side-effects?

 OPV causes almost no side-effects. Less than

1% of the people who receive the vaccine
develop a headache, diarrhoea, or muscle pain.
There is a very small risk of vaccine-
associated paralytic polio (VAPP), with
approximately two to four cases having been
reported for every one million children
immunized.

75
 Administration summary: OPV
 Type of vaccine: Live oral polio vaccine (OPV)
 Number of doses: Four in endemic countries (including
birth dose)
 Schedule: At birth*, 6, 10, 14 weeks
 Booster: Supplementary doses given during polio
eradication activities
 Contraindications: None
 Adverse reactions: VAPP very rarely (approximately 2 to 4
cases per million children vaccinated)
 Special precautions: Children known to have rare
congenital immune deficiency syndromes should receive
IPV rather than OPV.
76
 Dosage: 2 drops
 Injection site: –
 Injection type: –
 Storage: Store between 2°C and 8°C (maybe
frozen for long-term storage)
 * For polio endemic countries

77
 What is supplementary
?immunization with OPV
 A key strategy for polio eradication is
supplementary immunization with OPV. This is
usually conducted in large scale campaigns
(National Immunization Days) where two doses
of OPV, one month apart, are given to all
children under five years of age regardless of
how many doses they have received in the past.
 Many rounds of National immunization days
maybe conducted in a country however there is
no risk associated with receiving multiple doses
of OPV. 78
 Tuberculosis Vaccine (BCG) ]10
 What is BCG vaccine?
 BCG vaccine protects infants against tuberculosis. The
letters B, C, G stand for Bacille Calmette-Guérin. Bacille
describes the shape of a bacterium; Calmette and Guérin
are the names of the people who developed the vaccine.
 BCG vaccine comes in powder form. It must be
reconstituted with a diluent before use. It is essential that
only the diluent supplied with the vaccine be used.
 BCG vaccine should be kept at 2°C–8°C after
reconstitution. Remaining reconstituted vaccine must be
discarded after six hours or at the end of the
immunization session, whichever comes first.
79
 How safe is BCG vaccine and what are its
potential side-effects?
 Most children do have a reaction at the site of
injection. Normally, when BCG vaccine is
injected a small raised lump appears at the
injection site. This usually disappears within
30 minutes.
 After about two weeks, a red sore forms that
is about the size of the end of an unsharpened
pencil. The sore remains for another two
weeks and then heals. A small scar, about 5
mm across, remains. This is a sign that the
child has been effectively immunized. 80
 Other reactions include:
 Swelling or abscesses. Sometimes the glands in a
child’s armpit or near the elbow swell up after injection
with BCG vaccine, or he or she may develop an
abscess.
 Swollen glands or abscesses occur because an unsterile
needle or syringe was used, too much vaccine was
injected, or most commonly, the vaccine was injected
incorrectly under the skin instead of in its top layer.
 There are very few serious reactions following BCG
vaccine. Generalized infection due to BCG vaccination
occurs at a rate of five per million doses of vaccine
given, primarily in HIV-infected persons or those with
severe immune deficiencies.
81
Administration summary: BCG vaccine
 Type of vaccine: Live bacterial
 Number of doses: One
 Schedule: At or as soon as possible after birth
 Booster: None
 Contraindications: Symptomatic HIV infection
 Adverse reactions: Local abscess, regional lymphadenitis; rarely,
distant spread to osteomyelitis, disseminated disease
 Special precautions: Correct intradermal administration is essential.
A special syringe and needle is used for the administration of BCG
vaccine
 Dosage 0.05ml
 Injection site: Outer upper left arm or shoulder
 Injection type: Intradermal
 Storage: Store between 2°C–8°C (vaccine maybe frozen for long-
82
11] Meningococcal Vaccine

 What is meningococcal vaccine?

 There are two vaccines widely available that
protect against different types of
meningococcal meningitis. One protects
against types A, C, Y, and W-135 of the
disease, while the second protects against
types A and C. A third trivalent A, C, W
conjugate vaccine is currently being used in a
small number of countries but should become
more widely available soon.
83
 The conjugate vaccine links the
polysaccharide to a protein carrier. This
enables the vaccine to be more immunogenic
in infants and induces an immunological
memory which gives longer-lasting protection.
 The vaccines are packaged as a powder with
diluent in single and multi-dose vials. The
vaccine forms a clear liquid when
reconstituted (see Module 6).
84
 How safe is meningococcal vaccine and what are its
potential side-effects?
 Mild reactions include:
 Soreness. Some people experience redness or pain at
the injection site. These symptoms usually last one to
two days.
 Fever. A small percentage of people who receive the
vaccine develop a fever.
 Severe adverse reactions, including allergic reactions
(anaphylaxis, urticaria, wheeze, angioedema),
somnolence and neurological reactions (e.g., seizures,
paraesthesia and anaesthesia), have been reported very
rarely.
85
 Administration Summary: Meningococcal Vaccine
 Type of vaccine: Purified bacterial capsular polysaccharide
(AC, AC/W135, Y)
 Number of doses: One
 Schedule: older than three years recommended
 Booster: Every three to five years
 Contraindication: Severe adverse reaction to previous dose
 Adverse reactions: Occasional mild local reaction, mild
fever
 Special precautions: Children aged under two years of age
are not protected by the vaccine
 Dosage: 0.5 ml
 Injection site: Upper arm
 Injection type: Subcutaneous 86
 Yellow Fever (YF) Vaccine ]12

 What is YF vaccine?
 Yellow fever vaccine is recommended as part of the
routine national immunization programme in
countries where the disease is endemic. The vaccine
is a powder that must be reconstituted with diluent
provided before use (see Module 6). It is essential
that only the diluent supplied with the vaccine be
used. Reconstituted vaccine must be kept at 2C–
8°C and discarded after six hours or at the end of
the immunization session, whichever comes first.
87
 How safe is YF vaccine and what are its potential side-
effects?
 Mild reactions to the vaccine include:
 Headache, muscle pain, or mild fever. Fewer, than 5% of
people who receive YF vaccine develop these symptoms.
 Serious side-effects resulting from immunization are rare.
About 5–20 cases of anaphylaxis have been reported for every
one million doses of YF vaccine; the rate of true anaphylaxis is
likely to be much lower.
 Up to four cases of encephalitis per 100000 doses have been
reported in infants less than six months old for whom the
vaccine is not routinely recommended.
 If a serious reaction does occur, health workers should report
the problem to supervisors immediately.
 Those who have a severe reaction should not receive additional
doses. 88
 Administration summary: YF vaccine
 Type of vaccine: Live attenuated viral
 Number of doses: One dose
 Schedule: 9 months of age with measles vaccine
 Booster: International health regulations require a booster every 10
years
 Contraindications: Egg allergy; immune deficiency from medication
or disease; symptomatic HIV infection; hypersensitivity to previous
dose; pregnancy
 Adverse reactions: Hypersensitivity to egg; rarely, encephalitis in the
very young; hepatic failure. Rare reports of death from massive organ
failure
 Special precautions: Do not give before six months of age; avoid
during pregnancy
 Dosage: 0.5ml
 Injection site: Upper right arm
 Injection type: Subcutaneous 89
 Japanese Encephalitis (JE) Vaccine ]13
 What is JE vaccine?
 Three vaccines for preventing Japanese encephalitis are
currently available. However, as of 2003, none of these
vaccines are WHO pre-qualified. The most commonly
used one is a powdered vaccine that is mixed with a
diluent provided in a separate vial by the manufacturer.
 Before it can be used, JE vaccine must be reconstituted.
The reconstituted vaccine must be discarded after six
hours or at the end of the immunization session,
whichever comes first.
 Newer vaccines are becoming available in some areas.
Check your country’s policy.
90
 How safe is JE vaccine and what are its
potential side-effects?
 Mild reactions to the vaccine include:
 Soreness. About one in five people develop
tenderness, redness, and swelling at the
injection site.
 Fever, headache, nausea, and muscle pain.
These side-effects develop in about one in five
people who receive the vaccine. Many of these
side-effects last only a short time and can be
relieved with acetaminophen.

91
 The JE vaccine may cause severe delayed
allergic reactions. One case of serious allergic
reaction from the vaccine is reported for every
1000 to 100 000 doses given. These reactions can
occur within minutes or up to as many as nine days
after receiving an immunization.
 Allergic reactions may include hives, wheezy
breathing, or swelling of some part of the body.
Because of this, use of the vaccine requires careful
evaluation of risks and benefits.
 Patients must be advised to be near a health facility
for ten days after receiving the vaccine.
92
 Administration summary: JE vaccine
 Type of vaccine: Inactivated mouse-brain-derived
 Number of doses: Standard three-dose schedule
 Schedule:12 month. The interval between dose 1 and 2 should be 7
days and the 3rd dose should be given at day 30
 Booster: Most countries give a booster after one year, then three-yearly
 Contraindications: Hypersensitivity to previous dose
 Adverse reactions: Occasional mild local or systemic reactions;
serious allergic reaction including generalized urticaria, hypotension,
collapse occur 1/1000.
 Special precautions: JE vaccine not usually given under 12 months of
age
 Dosage: 0.5ml to child one to three years of age; 1.0 ml to child older
than three years
 Injection site: Upper arm
 Injection type: Subcutaneous
 Storage: Store between 2°C–8°C 93
Summary
Typical immunization schedule for children
Contra-indications to immunization
 There are not many contraindications to
immunization. All infants should be immunized
except in these three rare situations:
 Anaphylaxis or a severe hypersensitivity reaction
is an absolute contraindication to subsequent doses
of a vaccine. Persons with a known allergy to a
vaccine component should not be vaccinated.
 Do not give BCG or yellow fever vaccine to an
infant that exhibits the signs and symptoms of
AIDS.

94
 Note: an infant with known or suspected HIV
infection and/or signs and symptoms of AIDS
should receive measles vaccine at six months
and then again at nine months (refer to Module
6, Section 2).
 A second opportunity to receive a dose of
measles vaccine should be provided for all
children. This may be done either as part of
the routine schedule or in a campaign.
95
 If a reaction does occur, health workers
should report the problem to supervisors
immediately. Children who have a severe
reaction to a vaccine should not receive
additional doses of that vaccine.
 If a child has diarrhoea when you give OPV,
administer an extra dose – that is, a fifth dose
– at least four weeks after he or she has
received the last dose in the schedule.
96
 Giving vaccines at the same time:
 If you are giving more than one vaccine, do
not use the same syringe and do not use the
same arm or leg for more than one injection.
 Do not give more than one dose of the same
vaccine to a woman or child in one session.
 Give doses of the same vaccine at the correct
intervals. Wait at least four weeks between
doses of OPV, DTP, Hib, and Hep B vaccines.
97
 Other Vaccines
 Some countries have included vaccines other than
those described here in their national
immunization programmes, or may add them in
the future. These include Streptococcus
pneumoniae, typhoid fever, and cholera vaccines.
Ask your supervisor which vaccines are in your
national programme.
 New vaccines are always being studied. Research
is taking place to make vaccines more stable, to
combine them so that fewer injections are needed,
and to make them easier and safer to give.
98
 The following are not contraindications.
 Infants with these conditions should be immunized:
 Allergy or Asthma (except if there is a known allergy
to a specific component of the vaccine mentioned
above);
 Any minor illness, such as respiratory tract infections
or diarrhoea with temperature below 38.5°C;
 Family history of adverse events following
immunization;
 Family history of convulsions, seizures, or fits;
 Treatment with antibiotics;
99
 Known or suspected HIV infection with no signs and
symptoms of AIDS;
 Child being breastfed;
 Chronic illnesses such as chronic diseases of the
heart, lung, kidney, or liver
 Stable neurological conditions, such as cerebral palsy
or Down’s Syndrome;
 Premature or low-birth-weight (vaccination should
not be postponed);
 Recent or imminent surgery;
 Malnutrition; and History of jaundice at birth.
10
 Summary of Injection Sites
 Vaccine: Route of administration; Injection site
 BCG: Intradermal; Upper left arm
 DTP: Intramuscular; Outer mid-thigh
 OPV: Oral Mouth
 Hep B: Intramuscular; Outer mid-thigh
 Measles: Subcutaneous; Upper left arm
 Yellow fever: Subcutaneous; Upper right arm
 Tetanus toxoid: Intramuscular; Outer, upper arm
 Hib: Intramuscular; Infants – Outer mid-thigh; Older
children – Upper arm
 Japanese encephalitis: Subcutaneous; Upper arm
 Meningococcal: Subcutaneous; Upper arm
10
Unsatisfactory vaccines. Or (vaccination
sometimes fails to protect)
 Improper use (timing, route of
administration).
 Genetic differences between animals
 Antigenic differences
 Blocking by maternal antibodies
 Administration following infection
(exceptions - rabies)
 Counterfeit vaccines.
10
PNEUMOCOCCAL VACCINE
Rabies vaccine
ROTA VACCINE
PRESENTATIONS

10