Download 12Immuniz

IMMUNIZATION
1
IMMUNIZATION
• Immunization is a means of providing
specific protection against many common
and damaging pathogens by stimulating
an organism's immune system.
2
Milestones in immunization
3000BC
 Evidence
of sniffing
powdered small
pox crust in Egypt
2000BC
 Sniffing
of small
pox crust in China
1500BC
Turks introduce
variolation
1700AD
Introduction
of
variolation in England
and later in the US
3
Modern era of the vaccine
1885
Rabies vaccine
(Pasteur)
1920s
Diphtheria and
Tetanus
1934
Pertussis
1955
Salk polio
4
Modern era of the vaccine
1960s
1985
Mumps measles
and rubella virus
Sabin polio
Haemophilus
1990s
Hepatitis and
varicella
5
Pre- & post-vaccine incidence of
common preventable diseases
6
Different modes of acquiring
immunity
Immunity
Natural
Acquired
Passive Active Passive
Igs
IgG
Infection
Active
Vaccination
7
Passive Immunity
Natura
l
Artificia
l
Placental
transfer of IgG
Antibodies or
immunoglobulins
Colostral
transfer of IgA
Immune cells
8
Passive Immunization
disease
antibody
source
indication
diphtheria, tetanus
human, horse
prophylaxis, therapy
vericella zoster
human
immunodeficiencies
gas gangrene,
botulism, snake
bite, scorpion sting
horse
post-exposure
rabies,
human
post-exposure
hypogammaglobulinemia
human
prophylaxis
9
Advantages and Disadvantages of
Passive Immunization
Advantages
Disadvantages
no long term
protection
immediate
protection
serum sickness
risk of hepatitis
and Aids
graft vs. host
disease (cell
graft only)
10
Active Immunization
Natural
Artificial
Attenuated
organisms
killed organisms
exposure to subclinical infections
sub-cellular
fragments
toxins
others
11
Types of vaccines
• Killed vaccines: These are preparations of the normal (wild
type) infectious, pathogenic MO that has been rendered nonpathogenic, usually by chemical treatment such as with formalin
that cross-links viral proteins.
• Attenuated vaccines: These are live MO particles that grow in
the vaccine recipient but do not cause disease because the
vaccine virus has been altered (mutated) to a non-pathogenic
form; for example, its tropism has been altered so that it no
longer grows at a site that can cause disease.
• Sub-unit vaccines: These are purified components of the MO,
such as a surface antigen.
• DNA vaccines: These are usually harmless MO into which a
gene for a (supposedly) protective antigen has been spliced.
The protective antigen is then made in the vaccine recipient to
elicit an immune response
12
Advantages of attenuated vaccines
1. They activate all phases of immune system. They elicit
humoral IgG and local IgA (figure 8)
2. They raise an immune response to all protective antigens.
Inactivation, such as by formaldehyde in the case of the Salk
vaccine, may alter antigenicity
3. They offer more durable immunity and are more crossreactive. Thus, they stimulate antibodies against multiple
epitopes which are similar to those elicited by the wild type
virus
4. They cost less to produce
5. They give quick immunity in majority of vaccinees
6. In the cases of polio and adenovirus vaccines, administration
is easy
7. These vaccines are easily transported in the field
8. They can lead to elimination of wild type virus from the
community
13
Disadvantages of Attenuated
vaccine
1. Mutation. This may lead to reversion to
virulence (this is a major disadvantage)
2. Spread to contacts of the vaccinee who have
not consented to be vaccinated (This could
also be an advantage in communities where
vaccination is not 100%)
3. Spread of the vaccine virus that is not
standardized and may be mutated
4. Sometimes there is poor "take" in tropics
5. Live viruses are a problem in immunodeficiency
disease patients
14
Advantages of inactivated
(Killed) vaccine
1. They give sufficient humoral immunity if
boosters given
2. There is no mutation or reversion (This is
a big advantage)
3. They can be used with immuno-deficient
patients
4. Sometimes they perform better in tropical
areas
15
Disadvantages of inactivated
(Killed) vaccines
1. Some vaccinees do not raise immunity
2. Boosters tend to be needed
3. There us little mucosal / local immunity (IgA).
This is important (figure 8)
4. Higher cost
5. In the case of polio, there is a shortage of
monkeys
6. In the case of smallpox, there have been
failures in inactivation leading to immunization
with virulent virus.
16
Live Attenuated Vaccines
Polio (Oral) Sabin
not used in std.
schedule
measles, mumps
& rubella
Varicella zoster
hepatitis A
not required in
SC
yellow fever
Military and travelers
tuberculosis
children with no
history of chicken pox
17
Killed Whole-Organism Vaccines
Polio
Salk IM
influenza
Q fever
population at risk
typhoid, cholera, plague
elderly and at risk
epidemics and travelers
rabies
pertussis
post exposure
replaced by the
acellular vaccine
18
Microbial Fragment Vaccines
Bordetella. Pertussis
virulence factor protein
Haemophilus influenzae B
protein conjugated polysaccharide
Streptococcus pneumoniae
Polysaccharide mixture
Neisseria meningitidis
polysaccharide
19
Microbial Fragment Vaccines
Clostridium tetani (tetanus)
inactivated toxin (toxoid)
Corynebacterium diphtheriae
inactivated toxin (toxoid)
Vibrio cholerae
toxin subunits
Hepatitis B virus
cloned in yeast
20
Modification of Toxin to Toxoid
Toxin
Toxoid
chemical
modification
toxin moiety
antigenic determinants
21
Future Vaccines
22
NEW METHODS OF VACCINE
PRODUCTION
1.
2.
3.
4.
Selection for mis-sense
Synthetic peptides
Anti-idiotype vaccines
Recombinant DNA techniques
23
Selection for mis-sense
Conditional lethal mutants. Temperature-sensitive
mutants in influenza A and RSV have been made by
mutation with 5-fluorouracil and then selected for
temperature sensitivity. In the case of influenza, the
temperature-sensitive gene can be reassorted in
the laboratory to yield a virus strain with the coat
of the strains circulating in the population and the
inner proteins of the attenuated strain.
Cold
adapted mutants can also be produced in this way.
It has been possible to obtain mis-sense mutations
in all six genes for non-surface proteins.
24
Synthetic peptides
Injected peptides which are much smaller
than the original virus protein raise an IgG
response but there is a problem with poor
antigenicity. This is because the epitope
may depend on the conformation of the
virus as a whole. A non-viral example that
has achieved some limited success is a
prototype anti-malarial vaccine.
25
Anti-idiotype vaccines
An antigen binding site in an antibody is a reflection of the
three-dimensional structure of part of the antigen, that is of
a particular epitope. This unique amino acid structure in
the antibody is known as the idiotype which can be
thought of as a mirror of the epitope in the antigen.
Antibodies (anti-ids) can be raised against the idiotype by
injecting the antibody into another animal. This gives us an
anti-idiotype antibody and this, therefore, mimics part of
the three dimensional structure of the antigen, that is, the
epitope. This can be used as a vaccine. When the antiidiotype antibody is injected into a vaccinee, antibodies
(anti-anti-idiotype antiobodies) are formed that recognize a
structure similar to part of the virus and might potentially
neutralize the virus. This happens: Anti-ids raised against
antibodies to hepatitis B S antigen elicit anti-viral
antibodies.
26
27
Recombinant DNA techniques
1. Attenuation of virus
2. Single gene approach (Yeast)
3. Cloning of a gene into another virus
28
DNA VACCINES
• These vaccines are based on the
deliberate introduction of a DNA plasmid
into the vaccinee. The plasmid carries a
protein-coding gene that transfects cells in
vivo at very low efficiency and expresses
an antigen that causes an immune
response.
29
Advantages of DNA vaccines
1. Plasmids are easily manufactured in large amounts
2. DNA is very stable
3. DNA resists temperature extremes and so storage and transport are straight
forward
4. A DNA sequence can be changed easily in the laboratory. This means that we can
respond to changes in the infectious agent
5. By using the plasmid in the vaccinee to code for antigen synthesis, the antigenic
protein(s) that are produced are processed (post-translationally modified) in the
same way as the proteins of the virus against which protection is to be produced.
This makes a far better antigen than, for example, using a recombinant plasmid to
produce an antigen in yeast (e.g. the HBV vaccine), purifying that protein and
using it as an immunogen.
6. Mixtures of plasmids could be used that encode many protein fragments from a
virus or viruses so that a broad spectrum vaccine could be produced
7. The plasmid does not replicate and encodes only the proteins of interest
8. There is no protein component and so there will be no immune response against
the vector itself
9. Because of the way the antigen is presented, there is a cell-mediated response
that may be directed against any antigen in the pathogen. This also offers
protection against diseases caused by certain obligate intracellular pathogens
(e.g. Mycobacterium tuberculosis)
30
Possible Problems of DNA vaccines
1. Potential integration of plasmid into host
genome
leading
to
insertional
mutagenesis
2. Induction of autoimmune responses (e.g.
pathogenic anti-DNA antibodies)
3. Induction of immunologic tolerance (e.g.
where the expression of the antigen in
the host may lead to specific nonresponsiveness to that antigen)
31
Problems in vaccine development
• Different types of virus may cause similar diseases -- e.g.
the common cold. As a result, a single vaccine will not be
possible against such a disease
• Antigenic drift and shift -- This is especially true of RNA
viruses and those with segmented genomes
• Large animal reservoirs. If these occur, re-infection after
elimination from the human population may occur
• Integration of viral DNA. Vaccines will not work on latent
virions unless they express antigens on cell surface. In
addition, if the vaccine virus integrates into host cell
chromosomes, it may cause problems (This is, for
example, a problem with the possible use of anti-HIV
vaccines based on attenuated virus strains)
• Transmission from cell to cell via syncytia - This is a
problem for potential AIDS vaccines since the virus may
spread from cell to cell without the virus entering the
circulation.
• Recombination and mutation of the vaccine virus in an32
attenuated vaccine.
The eradication of smallpox
• There is no animal reservoir for variola, only humans
are infected by this virus
• Once a person has been infected by the virus, there
is lifelong immunity, although this may not be the
case with people immunized using the vaccine strain
• Subclinical cases rare and so an infected person can
be identified and isolated
• Infectivity does not precede overt symptoms, that is
there is no prodromal phase
• There is only one Variola serotype and so the vaccine
is effective against all virus strains
• The vaccine is very effective
• There has been a major commitment by the World
33
Health Organization and governments
Vaccination checklist
Here's a checklist of the vaccines that are routinely offered
to everyone in the UK for free on the NHS, and the age at
which you should ideally have them.
2 months:
Diphtheria, tetanus, pertussis (whooping cough), polio and
Haemophilus influenzae type b (Hib, a bacterial infection
that can cause severe pneumonia or meningitis in young
children) given as a 5-in-1 single jab known as
DTaP/IPV/Hib
Pneumococcal infection
34
‫جدول التطعيمات األساسية‬
‫الزيارة‬
‫الوالدة‬
‫شهرين‬
‫شهور ‪4‬‬
‫شهور ‪6‬‬
‫شهور ‪9‬‬
‫شهر ‪12‬‬
‫شهر ‪18‬‬
‫شهر ‪24‬‬
‫سنوات ‪4-6‬‬
‫‪35‬‬
‫اللقاح‬
‫‪Basic Vaccination Schedule‬‬
‫‪Vaccine‬‬
‫‪Vaccination checklist‬‬
‫الدرن‬
‫‪BCG‬‬
‫اإللتهاب الكبدي (ب)‬
‫‪HepB‬‬
‫شلل األطفال المعطل‬
‫‪IPV‬‬
‫)الثالثي البكتيري ؛ اإللتهاب الكبدي (ب) ؛ المستدمية النزلية(‬
‫) ‪( DTP , HepB‬‬
‫شلل األطفال الفموي‬
‫‪OPV‬‬
‫)الثالثي البكتيري ؛ اإللتهاب الكبدي (ب) ؛ المستدمية النزلية(‬
‫)‪(DRP , HepB , Hib‬‬
‫شلل األطفال الفموي‬
‫‪OPV‬‬
‫)الثالثي البكتيري ؛ اإللتهاب الكبدي (ب) ؛ المستدمية النزلية(‬
‫)‪(DRP , HepB , Hib‬‬
‫الحصبة المفرد‬
‫)‪Measles (mono‬‬
‫شلل األطفال الفموي‬
‫‪OPV‬‬
‫الثالثي الفيروسي‬
‫‪MMR‬‬
‫الجديري المائي‬
‫‪Varicella‬‬
‫شلل األطفال الفموي‬
‫‪OPV‬‬
‫)الثالثي البكتيري ؛ المستدمية النزلية(‬
‫) ‪( DTP m HibH influenzae type B‬‬
‫اإللتهاب الكبدي (أ)‬
‫) ‪Hepatitis ( A‬‬
‫اإللتهاب الكبدي (أ)‬
‫) ‪Hepatitis ( A‬‬
‫شلل األطفال الفموي‬
‫‪OPV‬‬
‫الثالثي البكتيري‬
‫‪DTP‬‬
‫الثالثي الفيروسي‪ +‬الجديري المائي‬
‫‪MMR, Varicella‬‬
‫‪Visit‬‬
‫‪At Birth‬‬
‫‪2 months‬‬
‫‪4 months‬‬
‫‪6 months‬‬
‫‪9 months‬‬
‫‪12 months‬‬
‫‪18 months‬‬
‫‪24 months‬‬
‫‪4-6 years‬‬
Adverse Events Occurring
Within 48 Hours DTP of Vaccination
Event
local
redness, swelling, pain
systemic: Mild/moderate
fever, drowsiness, fretfulness
vomiting
anorexia
systemic: more serious
persistent crying, fever
collapse, convulsions
acute encephalopathy
permanent neurological deficit
36