Vaccines & Immunization

Vaccines
• What is Vaccine?
Vaccine is harmless agent perceived as enemy.
Vaccines are molecules but not necessarily
protein that elicits an immune response.
• Even 2,500 Years Ago, People Knew Immunity
Worked.
• Greek physicians noticed that people who
survived smallpox never got it again.
• The insight: Becoming infected by certain
diseases gives immunity.
 HISTORY OF VACCINE

• The technique of
variolation was improved
by Edward Jenner in 1798.
• He introduced fluid from
cow pox pustule into eight
year old boy.
• As a result, after a world-
wide effort Smallpox was
eliminated as a human
disease in 1978
 HISTORY OF VACCINE

• In 1880 Louis
Pasteur recognized
that aging has
weakened the
virulence of
pathogen.
• Vaccine against
Anthrax in 1881.
First human vaccine in 1885.
 What Vaccines do?
• Provide immunity
State of protection from
infectious disease
• Kinds of Immunity.
– Active immunity
– Passive immunity
 How does vaccine work?
• Step 1:-Vaccine

• Step 2:-Immune cells

• Step 3:-B cells

• Step 4:- Helper CD4 T Cells

• Step 5:-Memory cells

It Response of immune system to vaccine
 Creating a new vaccine
– Consider a new infectious agent as X.
– Examine how it cause disease.
– Geneticists analyze X genes.
– Immunologists would explore how immune
response to X agent.
– Identify antigen X that best stimulate the immune
response.
– Find either toxin secreted by it or not.
– Once scientist had some basic information about
X he would try to develop a vaccine against it.
 Vaccine - Ideal characteristics
– Excellent safety profile

– Single dose administration

– Offers protection for a long time

– Low cost

– Stability and ease of administration.

– Works against a wide range of different strains

 Types of vaccine

– Inactivated or 'killed' vaccines

– Live attenuated vaccines
– Toxoid vaccines
– Antigen/ Subunit vaccines
– Polysaccharide vaccines
– Conjugate vaccines
– Synthetic Peptide vaccines
– DNA vaccines
– Recombinant vector vaccines
 Inactivated or 'killed' vaccines

• Definition:-
An inactivated or killed vaccine is produced
by killing disease causing agents with
chemicals, heat or radiation.
– More safer
– Need to maintain structure of epitope during
inactivation
– Chemical activation by formaldehyde.
• Examples:-
Salk Polio vaccine, whooping cough vaccine,
Hepatitis A vaccine and influenza vaccine
Advantages of inactivated vaccines
• Givessufficient humoral immunity if boosters given
• No mutation or reversion
• Can be used with immuno-deficient patients

Disadvantages of inactivated vaccines

• Many vaccines do not raise immunity
• Boosters needed.
•Not provide cell mediated immunity
•Higher cost
•Failure in inactivation and immunization with virulent virus
 Attenuated vaccine

– Definition:-Attenuated vaccine consist of version

of living microorganism that has been weakened
in the lab.
– Attenuation is usually achieved by passing of virus
in foreign host such as embryonated eggs or tissue
culture cell.
– Examples:-
Vaccines against Rotavirus, Yellow fever, Sabin
Polio Mumps and Measles
 Sabin Polio Vaccine
– To produce Sabin Polio vaccine, attenuation
is achieved with high inocula and rapid
passage in primary monkey kidney cells.
– The virus population became overgrown
with a less virulent strain that can have lost
the ability to grow in human nervous system.
– Non-virulent strain of all three polio types
have been produced for the vaccine.
– Mechanism of working of Sabin Polio vaccine
Advantages of Attenuated Vaccines
• Activates all phases of immune system. Can get humoral IgG and
local IgA

• Raises immune response to all protective antigens. Inactivation

may alter antigenicity.

• More durable immunity; more cross-reactive.

• Quick immunity in majority of vaccines

• In case of polio and adeno vaccines, easy administration

• Easy transport in field

• Can lead to elimination of wild type virus from the community

Disadvantages of Live Attenuated Vaccine

• Mutation; reversion to virulence (often frequent)

•Spread vaccine not standardized--may be back-mutated

20
• Poor "take" in tropics

• Problem in immunodeficiency disease (may spread to

these patients)
 Toxoid Vaccine
• Definition:-
Toxoid vaccines are made by treating toxin or
poisons produced by germs with heat or
chemical such as formalin to destroy their
ability to cause illness.
• Don't cause disease but stimulate immune
responses.
• Examples:-
• Vaccines against Tetanus and Diphtheria
 Limitations of toxoid vaccine

– One of the problem with vaccines consisting

of purified macromolecule is the difficulty of
obtaining sufficient quantities of the purified
starting materials.

– In case of diphtheria this limitation has been

solved by cloning the exotoxin.
 Antigen or Subunit vaccine
• Definition:-
Subunit vaccine only contain antigens that best
stimulate the immune system.
• These vaccines use epitopes
• Advantage of Subunit vaccine
• As they contain only antigen not other molecules
of microbe so the chance of adverse reaction is
lower.
• Examples:-
• Vaccine against Hepatitis B.
 Hepatitis B
• Hepatitis B vaccine contain one of the viral
envelop protein, hepatitis B surface antigen
(HBsAg). Three vaccine injection are given with
the second injection at lest one month after the
first dose and the 3rd injection given six month
after first dose.

• Afterward an immune system antibody to HBsAg

is established in the blood stream which then
provide immunity to Hepatitis B infection.
Hepatitis B Structure
 Polysaccharide vaccine
• The virulence of some pathogenic bacteria depends
primarily on the antiphagocytic properties of their
hydrophilic polysaccharide capsule.
• Coating of capsule with antibodies or complement
greatly increase the ability of macrophage and
neutrophils to phagocytize such pathogens.
• Example:- streptococcus pneumoniae consist of 23
antigenically different capsular polysaccharides.
• Limitation:-
• Inability to activate T helper cells.
• So to involve T helper cells is to link polysaccharides
antigen to a carrier protein.
 Conjugate vaccine
• Definition:- A conjugate vaccine is created by
covalently attaching poor antigen to a carrier
protein, thereby conferring the immunological
attributes of the carrier on the antigen surface.
• This technique for the creation of effective
immunogen is most often applied to bacterial
polysaccharides for the prevention of invasive
bacterial disease.
• Example:-
• Vaccine against Hib
 Conjugate vaccine
Bacteria
Carrier
protein

Polysaccharide linked to
carrier protein
Polysaccharide
(sugar) coating
 Need of Conjugate vaccine
• The shortcomings of the polysaccharide vaccine lead
to the production of the Hib polysaccharide-protein
conjugate vaccine. Attaching Hib polysaccharide to a
protein carrier greatly increased the ability of the
immune system of young children to recognize the
polysaccharide and develop immunity.
• There are currently three types of conjugate vaccine
utilizing different proteins in the conjugation process,
all of which are highly effective:
– Tetanospasmin(also called tetanus toxin),
– Mutant diphtheria protein,
– Meningococcal group B outer membrane protein.
 Synthetic Peptides Vaccines
• The development of synthetic peptides that might be useful as
vaccines depends on the identification of immunogenic sites.
• The best known example is foot and mouth disease, where
protection was achieved by immunizing animals with a linear
sequence of 20 amino acids.
• Synthetic peptide vaccines would have many advantages:
– Their antigens are precisely defined and free from unnecessary
components which may be associated with side effects.
– They are stable and relatively cheap to manufacture.
– Furthermore, less quality assurance is required.
– Changes due to natural variation of the virus can be readily
accommodated, which would be a great advantage for
unstable viruses such as influenza.
 Dna vaccine
• These vaccines are based on the deliberate
introduction of a DNA plasmid into the vaccine.
• The plasmid carries a protein-coding gene that
transfect cells in vivo at very low efficiency and
expresses an antigen that causes an immune
response.
• These are often called DNA vaccines but would better
be called DNA-mediated or DNA-based immunization
since it is not the purpose to raise antibodies against
the DNA molecules themselves but to get the protein
expressed by cells of the vaccine.
• Usually, muscle cells do this since the plasmid is given
intramuscularly.
• It should be noted that the plasmid does not replicate
in the cells of the vaccine, only protein is produced.
 Dna vaccine
• Route of administration of DNA vaccines:-
• It has also be shown that DNA can be introduced into
tissues by bombarding the skin with DNA-coated gold
particles.
• It is possible to introduce DNA into nasal tissue in nose
drops.
• In the case of the gold bombardment method, one
nanogram of DNA coated on gold produced an
immune response.
• One microgram of DNA could potentially introduce a
thousand different genes into the vaccine.
 Advantages of dna vaccines
– Plasmids are easily manufactured in large amounts
– DNA is very stable
– DNA resists temperature extremes and so storage and
transport are straight forward
– A DNA sequence can be changed easily in the
laboratory. This means that we can respond to
changes in the infectious agent
– 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
 Advantages of dna vaccines
– The plasmid does not replicate and encodes only
the proteins of interest
– There is no protein component and so there will
be no immune response against the vector itself
• Disadvantages of DNA vaccines:-
– Only protein antigens can be coded there is no
DNA vaccine against those bacterial infections
which have protective polysaccharide act as
antigen.
– Examples:-Vaccine against Flu
 Recombinant vector vaccine
• Definition:- Recombinant vector vaccine use an
attenuated virus or bacterium to introduce
microbial DNA to cells of the body.
• In nature, viruses latch on to cells and inject their
genetic material into them.
• In the lab, scientists have taken advantage of this
process. They have figured out how to take the
roomy genomes of certain harmless or
attenuated viruses and insert portions of the
genetic material from other microbes into them.
• The carrier viruses then Carry that microbial DNA
to cells.
• Recombinant vector vaccines closely mimic a
natural infection and therefore do a good job of
stimulating the immune system.