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Vaccines

 RITU SINGH
IMMUNIZATION
 Immunizationñ or immunisationñ is the
process by which an individual's immune
system becomes fortified against an agent
(known as the immunogen).
 Immunization can be achieved in an active
or passive fashion:
1. Active Immunization
2. Passive immunization
ACTIVE IMMUNIZATION
 Active immunization entails the
introduction of a foreign molecule into the
bodyñ which causes the body itself to
generate immunity against the target. This
immunity comes from the T cells and the B
cells with their antibodies.
 VACCINES are used for active
immunization.
PASSIVE IMMUNIZATION
 Passive immunization is where pre-synthesized
elements of the immune system are transferred
to a person so that the body does not need to
produce these elements itself.
 Currentlyñ antibodies can be used for passive
immunization. This method of immunization
begins to work very quicklyñ but it is short
lastingñ because the antibodies are naturally
broken downñ and if there are no B cells to
produce more antibodiesñ they will disappear.
Contd.
 Passive immunization occurs
physiologicallyñ when antibodies are
transferred from mother to fetus during
pregnancyñ to protect the fetus before and
shortly after birth.
ghat 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.
The Mechanism of a Vaccine
 In an ideal scenarioñ whenever
a vaccine is first administeredñ
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
cellsñ which become helper T
cells (Th cells).
 Grom thereñ the activated Th
cells goes on to activate
mature B-cells.
 These activated B-cells divides
into two cell typesñ antibody-
producing plasma cells andñ
most importantlyñ memory B
cells.
 Memory T-cells are also
establishedñ howeverñ they
usually have a shorter half-life
than memory B cellsñ thusñ
they play only a minor role in
long-term immunity.
 Usuallyñ there are no cytotoxic
T-cells formed whenever the
body responds to a vaccine.
Potential Shortcomings of Vaccines
 In some rare casesñ a vaccine may
directly activate a B cellñ 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.
 Thusñ such a vaccine will be
useless against establishing
immunity.
 Sometimesñ the vaccine may be cleared from the body before it has
the chance to properly stimulate the immune system.

 Some pathogensñ particularly virusesñ has a tendency to mutate and


change there surface antigensñ making a vaccine against them
ineffective.

 This is especially true of malariañ which is constantly changing its


surface antigens.

 Several different types of pathogens may cause similar infectionsñ


thusñ several different vaccines may be required for them.

 Gor exampleñ Heamophilus influenzaeñ a bacteriumñ and influenzavirusñ


a virusñ causes diseases with similar symptoms.
The Importance of the Secondary Immune Response

 During the secondary immune responseñ the body mounts a


quickerñ more robust attack on the pathogen.
 Thusñ the pathogen is cleared from the body before it has the
chance to cause an infection.
Adjuvants
 An adjuvant is a
chemical substance
that can be added to a
vaccine in order to
enhance the immune
response to the
vaccine.
Routes of Administration
 There are three different routs
of administration:
 Intradermal administration.
 Three types are intravenousñ
intramuscularñ and
subcutaneous.
 Oral administration.
 Vaccine is usually given in
liquid form.
 Goodsñ such as tomatoesñ
have been engineered to
produce a vaccine.
 Intranasal administration.
Boosters
 Gor most vaccinesñ the
immunity against a particular
pathogen has a tendency to
wear off over time.
 In this caseñ a periodic
³booster´ 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.
Types of Vaccines
 Live
attenuated

 Inactivated

 Toxoid
Inactivated Vaccines fall into different
categories
1. Whole
 viruses
 bacteria
Ñive Attenuated Vaccines
also have several disadvantages
 Severe reactions possible
especially in
immune compromised
patients

 gorry about recreating


a wild-type pathogen
that can cause disease

 Gragile ± must be
stored carefully
A number of the vaccines you received
were live Attenuated Vaccines
 Viral : measlesñ mumpsñ rubellañ
vacciniañ varicella/zosterñ
yellow feverñ rotavirusñ
intranasal influenzañ oral polio
 Bacterial: BCG (TB)ñ oral typhoid
Inactivated Vaccines are the other
option
½luses
 Vo chance of recreating live pathogen
 Ñess interference from
circulating antibody than
live vaccines
Inactivated Vaccines are the other
option
Minuses
 aannot replicate and thus generally not as
effective as live vaccines
 Usually require 3-5
doses
 Immune response
mostly antibody based
Inactivated Vaccines are also
a common approach today
Whole-cell vaccines
 Viral polioñ hepatitis Añ
rabiesñ influenza
 Bacterial pertussisñ typhoidñ
cholerañ plague
½ ÑI VAaaIV IÑÑUSTRATS
TH ½ÑUSS AV IVUSS 
ÑIV VAaaIVS
Sabin Polio Vaccine
 Attenuated by passage in foreign host
(monkey kidney cells)
 Selection to grow in new host makes
virus
 less suited to original host
Sabin Polio Vaccine
 Attenuated by passage in foreign host (monkey
kidney cells)
 Selection to grow in new host makes virus
 less suited to original host

 Grows in epithelial cells


 oes not grow in nerves
 Vo paralysis
 Ñocal gut immunity (IgA)
Salk Polio Vaccine
 ormaldehyde-fixed
 Vo reversion
Toxoids Vaccines
 Some species of bacterial
produce what is known as
exotoxens.
 Toxoids are vaccines which
consist of exotoxins that have
been inactivatedñ either by heat
or chemicals.
 These vaccines are intended to
build an immunity against the
toxinsñ but not necessarily the
bacteria that produce the
toxins.
 Some examples are botulinum
antitoxen and diphtheria
antitoxen.
Other vaccines
Anti-Idiotype Vaccines
 In this unique type of vaccineñ
antibodies from a sick individual are
isolated.
 These antibodies are then injected into
a lab animalñ 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 individualñ 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 pathogenñ the individual
will have an immunity against that
pathogen.
DNA Vaccines
 DNA vaccines consist of plasmids that contains genes for certain types
of antigens.
 Once administeredñ 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.
Chimeric Vaccines
 Chimeric vaccines usually consist of attenuated viruses
that have been engineered to carry antigens from multiple
types of pathogens.
 Gor exampleñ the yellow fever vaccine YG17D has been
engineered to carry antigens from HIVñ different types of
bacteriañ malariañ even cancer.
 The main of a chimeric vaccine is the establishment of
immunity against several different diseases with one
administration.
Approaches to make recombinant
vaccines

Clone gene from


virus or bacteria
and express this
protein antigen
in yeastñ bacteria or
mammalian cells in
culture
Approaches to make recombinant
vaccines
2. Clone gene from
virus or bacteria
Into genome of another
virus (adenovirusñ
canary poxñ vaccinia)
And use this live virus
as vaccine
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
vaccinesñ only one method will work.
In-Vivo
 In in-vivo manufacturingñ the
vaccine is produced inside a living
organism.
 Embryonated Chicken eggs are
are commonly usedñ particularly
in producing flu vaccines.
 Vaccinesñ such as anti-idiotypeñ
can also be produced in lab
animalsñ such as mice.
 There are even some species of
plantñ such as bananasñ that have
been genetically engineered to
produce a vaccine.
In-Vitro
 Hereñ using recombinant DNA
technologyñ vaccines can be
produced in yeast culturesñ
bacterial culturesñ or cell
cultures.
 Recombinant vaccinesñ such as
chimeric vaccinesñ are
produced in this manor.
 Attenuated virus/bacteria
vaccines can also be produced
this way.
Chemical Synthesis
 Hereñ instead of using
biological systems to
produce a vaccineñ a vaccine
can be produced in a lab.
 Vaccines that utilize
synthetic peptides as well as
conjugated lipids and
polysaccharides are
manufactured this way.
 Usuallyñ this method is used
in combination with either
in-vivo or in-vitro
production.
Risks Associated gith Vaccines
 The primary risk associated with vaccinesñ especially vaccines that
utilize live organismsñ is that the vaccine itself causes illness.
 This Happened with the orally administered Sabin vaccine for
polioñ where some individuals became ill andñ in rare casesñ
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 vaccineñ especially vaccines produced in embrionated chicken
eggs and in transgenic plants.
THAV Y U VRY UaH!!