Chapter 12

Vaccines

 Markos N.
 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.
 Introduction to Vaccines
• Vaccines –
– Biological substances that stimulate the host’s
(animal) immune system

– Are designed to produce an immune response

identical to that produced by the natural
infection.

• Vaccines can Prevent the debilitating and, in some

cases, fatal infectious diseases.
 Introduction to Vaccines
• Help to eliminate the illness and disability of polio,
measles, and rubella

• Vaccines protect the

– Vaccinated individual,
– Protect society.

• A community with many vaccinated people

– Protects the few who cannot be vaccinated—such
as young children.
 Introduction to Vaccines
• Indirectly protects unvaccinated from exposure to
disease = HERD IMMUNITY

• Aim of an ideal vaccine:

– To produce the same immune protection which
usually follows natural infection but without
causing disease
– To generate long-lasting immunity
– To interrupt spread of infection
 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).
 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.
 Criteria for Effective Vaccines
• WHO has stated that the ideal vaccine would
have the following properties:
– Affordable worldwide
– Heat stable
– Effective after a single dose
– Applicable to a number of diseases
– Administered by a mucosal route
– Suitable for administration early in life
 Types of Immunity

• Active Immunity
- Naturally-Acquired Active Immunity
- Artificially-Acquired Active Immunity

• Passive Immunity
- Naturally-Acquired Passive Immunity
- Artificially-Acquired Passive Immunity
 Immunity

Specific defenses
Immunity

Active immunity Passive immunity

Following clinical infection natural Transfer of maternal

Antibodies Through placenta

Following subclinical infection Transfer of maternal

Antibodies Through milk
acquired
Following vaccination Following administration of
Immunoglobulin or antiserum
 Active Immunity
• Resistance developed in response to stimulus by an antigen
(infecting agent or vaccine) and is characterized by the
production of antibodies by the host immune system.

• May acquired through naturally or artificially:

• Naturally acquired through disease
• Artificially acquired through vaccination
– Vaccines include inactivated toxins, killed microbes, parts
of microbes, and viable but weakened microbes.
 Active immunity is usually permanent
• A vaccinated person has a secondary response
based on memory cells when encountering the
specific pathogen.
– Routine immunization against infectious diseases such
as measles and whooping cough, and has led to the
eradication of smallpox, a viral disease.
– Unfortunately, not all infectious agents are easily
managed by vaccination.
• HIV vaccine in the works
• .
 Active Immunization

• Limitations of Artificially Active immunity

– developing an immune response does not =
achieving state of protective immunity (may
only Ab/CMI)
– vaccine can induce primary response but fail to
induce memory cells = host unprotected

• Various approaches used to effectively induce

humoral and cell-mediated immunity and the
production of memory cells.
 Passive Immunity
• Passive Immunity- Protection against disease
through antibodies produced by another human
being or animal. (here antibodies are prepared from
outside the host)
• Effective, but temporary
• May be acquired in to two ways:
A. Naturally acquired passive imm.: a condition
when preformed Igs become transferred from
the immunized mother to the new born infant.
Ex. Maternal antibodies from colostrums and
transplacental
B. Artificially acquired passive imm.: can be
transferred artificially by injecting antibodies
from an animal that is already immune to a
disease into another animal.

– Rabies treatment: injection with antibodies against

rabies virus
 Designing Vaccines for Active
Immunization
• Many common vaccines use
– inactivated (killed), but still antigenic or
– live/altered – attenuated microorganisms.
• Caused to loose pathogenicity (cultured in
abnormal conditions)
– Immunogenic substance (e.g., protein,
polysaccharide) from pathogen, capable of
producing an immune response
• DNA vaccines currently being tested for human
use
 Whole organism vaccines
• Attenuated organisms, for vaccines, lose ability
to cause significant disease (pathogenicity)

– to attenuate, grow a pathogenic bacterium or

virus for prolonged periods under abnormal
culture conditions

– retains capacity for short term growth within

inoculated host.
 Attenuated preparations permits
–increased immunogenicity and
–production of memory cells
–often require only a single immunization

– A major disadvantage is the possibility that they

will revert to a virulent form.
 Purified Macromolecules as
Vaccines

• Derived from pathogens.

• Are specific, purified macromolecules

• Avoid some risks associated with attenuated or

killed whole organism vaccines.
• Three general forms of such vaccines are in current
use:

– inactivated exotoxins,
– capsular polysaccharides, and
– recombinant microbial antigens
Purified Macromolecules as
Vaccines
 Purified Macromolecules as
Vaccines
• Isolate gene encoding immunogenic protein, clone
it, and express/insert in bacterial, yeast, or
mammalian cells using recombinant DNA
technology.

• Example for human use is hepatitis B vaccine

developed by cloning the gene for surface antigen
of hepatitis B virus (HBsAg) and expressing it in
yeast cells.
.
• The recombinant yeast cells are grown in large
fermenters, and HBsAg accumulates in the
cells.

• The yeast cells is disrupted, releases the

recombinant HBsAg, which is purified by
biochemical techniques
 Recombinant-Vector Vaccines

• Genetic engineering techniques are a way to

attenuate a virus irreversibly by selectively
removing genes that are necessary for virulence.

• Genes encoding major antigen of virulent

pathogens can be added in high levels to
attenuated viruses or bacteria.
• The attenuated organism serves as a vector,
replicating within the host and expressing the
gene product of the pathogen.

• Vaccinia virus, attenuated vaccine used to

eradicate smallpox, was widely employed as a
vector vaccine.
Recombinant-Vector Vaccines

Source: Kuby Immunology 2007, 5th ed

 DNA Vaccines Recombinant-Vector Vaccines
• Plasmids are easily manufactured in large
amounts

• DNA is very stable, resists temperature

extremes so storage and transport are straight
forward

• DNA sequence can be changed easily in the

laboratory. So can respond to changes in the
infectious agent
• The DNA is injected into a person’s muscle. It
integrates into the sysnthesis of the muscle
cell, stimulating a strong Tc cell response with
good memory
 DNA Vaccines

Gene for
antigen

plasmid Muscle cell

Muscle cell expresses protein; antibody’s made; & CTL response

 DNA Vaccines

DNA vaccines produce a situation that reproduces

a virally-infected cell
Gives:
• Broad based immune response
• Long lasting CTL response
 DNA Vaccines
• Potential Risks
– Potential integration of plasmid into host
genome leading to insertional mutagenesis

– Induction of autoimmune responses (e.g.

pathogenic anti DNA antibodies)

– Induction of immunologic tolerance (e.g.

where the expression of the antigen in the host
may lead to specific non-responsiveness to that
antigen)
 DNA Vaccines Recombinant-Vector Vaccines
Multivalent Subunit Vaccines
• A method for constructing synthetic peptide
vaccines that contain both immunodominant
for both
– B-cell and
– T-cell epitopes.

• If a CTL response is desired, vaccine must be

delivered intra-cellularly so that the peptides
can be processed and presented together with
class I MHC molecules.
 Multivalent Subunit Vaccines
• Techniques to develop multivalent vaccines that
present multiple copies of a given peptide or a
mixture of peptides

• different specificity monoclonal antibodies on

solid matrix, permits binding a mixture of peptides
or proteins
– provides immunodominant epitopes for both T
cells and B cells

– multivalent complexes shown to induce vigorous

humoral and cell-mediated responses.
Multivalent Subunit Vaccines
 Summary
• A state of immunity can be induced by passive or
active immunization
– a) Short-term passive immunization is induced
by transfer of preformed antibodies.
– b) Infection or inoculation achieves long-term
active immunization.

• Three types of vaccines are currently used in

humans:
– attenuated (avirulent) microorganisms,
– inactivated (killed) microorganisms, or
– purified macromolecules.
 Summary
• Protein components of pathogens expressed in
cell culture may be effective vaccines.

• Recombinant vectors, including viruses or

bacteria, engineered to carry genes from
infectious microorganisms, maximize cell-
mediated immunity to the encoded antigens

• Plasmid DNA encoding a protein antigen from a

pathogen can serve as an effective vaccine
inducing both humoral and cell-mediated
immunity.
Summary

Source: Kuby Immunology 2007 5th ed

Thank you!!