Vaccines

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Ch1.Infections and Vaccines
 Ch1.Infections and Vaccines
HOW ORGANISMS EVADE THE IMMUNE RESPONSE
Viruses
Small RNA viruses, such as influenza and HIV
small genomes  so can not encode proteins to
evade the immune response.
•BUT their RNA genome tends to mutate, 
RNA virus antigenic proteins change
continually evade immunologic memory.
• HIV this can happen within an individual.
over just a few months of infection.
•Influenza mutates more slowly across a
population rather than in an individual.
DNA viruses are larger and have capacity in
their genomes for evasion tools.
•Some DNA viruses (members of the herpes virus
family)evade the adaptive immune response
by downregulating (MHC) expression, and the
innate response is required for their control 2
(natural killer [NK] cells).
 Bacterial pathogens different strategies to evade:
 Extracellular : Pneumococcus (Streptococcus pneumoniae)
and Haemophilus sp. evade the innate response (opsonization by
complement and phagocytosis) by producing
a polysaccharide capsule 
successful pathogens of the respiratory tract.

 Intracellular:
• Mycobacteria, such as M. tuberculosis,
 have waxy coats that block the effects
of phagocyte enzymes.
 They also secrete catalase, which
inhibits the effects of the respiratory burst.
• Listeria
 cause meningitis, particularly in pregnant women.
Listeria secrete listeriolysin, which punches holes
in the phagolysosome walls.
The bacteria can then escape into the cytoplasm, where they are not
exposed to the toxic products of the metabolic burst or to proteolytic
enzymes. 3
Ch1.Infections and Vaccines
 Mechanism of Immunity
• Most primary infections ( except TB, HIV, herpes viruses)are completely
cleared by the immune system sterilizing immunity.
• Immunologic memory develops subsequent exposure to the same pathogen
elicits a memory response by the adaptive immune system so
infection is prevented or symptoms reduced.
• After maternal antibody lost early childhood  a series of primary infections
while effective immunologic memory is developed.
• Vaccination can act as a substitute for primary infection allowing
immunologic memory to develop without a symptomatic primary infection.
• Vaccines are a success story; smallpox completely eradicated .
• Many other infections (polio, diphtheria & pertussis) become relatively rare.
• Passive immunotherapy the transfer of adaptive immunity-usually
antibodies-from one individual to another give protective antibodies to an
individual exposed to a pathogen.
• Some cases might need  both
- passive immunotherapy (to reduce the immediate risk of infection) and
- the vaccine (to induce immunologic memory and reduce the risk for future
Ch1.Infections and Vaccines 4
infection).
Ch1.Infections and Vaccines 5
 Strategies for vaccine development

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• Antigen in form of infection or Vaccine develops Active
Immunity Immunologic immunity develops and  protects
individual from reinfection.
• There are various types and compositions of vaccine
• Most vaccines elicit antibodies, and some elicit T-cell responses.
Antibodies 
 Can be neutralizing antibodies prevent pathogens from binding onto
target cells or prevent the actions of toxins released from pathogens
 Another Antibodies activate complement, and stimulate phagocytosis
and NK cell-mediated killing.
CD8+ T cells inhibit viral replication by secreting interferons or,
more often, kill infected cells.
 Types of Vaccines:
 Live Vaccines
Killed Organisms
Subunit Vaccines
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Ch1.Infections and Vaccines
• Live Vaccines (Viruses or Bacteria)
First discovered and the most effective ones.
very successful smallpox and polio are live
vaccines.
use non virulent organisms (organisms that have
evolved to grow in animals); although they
replicate in healthy vaccine recipients, they do not
cause disease.
Live vaccines are very effective for three reasons
1. They replicate and thus deliver sustained doses of antigen.
2. They replicate intracellularly so they deliver antigenic peptides to (MHC)
class I stimulate cytotoxic T cells (CTLs).
3. They replicate at the anatomical site of infection, further focusing the
immune response live vaccines given by nose or by mouth elicit IgA Abs.
Attenuated live vaccines cause serious infections immunodeficiency patients
Occasionally, live vaccines viruses may spontaneously revert to the virulent wild-
type organism.
Attenuated polio vaccine differs from wild-type virus in 10bp make it easy for the
virus to mutate back to the virulent form. This has been identified in water
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supplies. So USA has started to use killed polio vaccine once more.Ch1.Infections and Vaccines
Ch1.Infections and Vaccines 9
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Killed Organisms (Viruses or Bacteria)

Generally not as effective as live vaccines
at eliciting a protective immune response.
Theoretically much safer Killed vaccines
- do not replicate in hosts and
- cannot enter intracellular antigen
presenting pathways.

Subunit Vaccines (Toxoids, recombinant,

polysaccharides and DNA)
 Subunits are components of pathogens
induce predominantly antibody responses.
Can be prepared by destroying virulent
organisms, purifying the subunit,
and then inactivating it  so that it cannot
cause disease.
Other subunits are prepared using
recombinant technology.
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Toxoids: Subunits purified from organisms and then inactivated
 usually bacterial exotoxins chemically altered to
make them safe.
The neutralizing antibodies produced block the
effects of the toxins.
Diphtheria and tetanus toxoid are good examples
Subunit and toxoid vaccines of low immunogenicity compared with intact
organisms, and they may need adjuvants to work effectively.

Recombinant Virus
Hepatitis B vaccine is a subunit antigen that has been produced
using recombinant techniques (made up of recombinant virus
surface peptide)
 Antibodies raised against surface peptide will prevent the virus
attaching to and then entering liver cells.
Up to now, hepatitis B vaccine has been very effective.

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 Recombinant Virus vaccine
Hepatitis B vaccine

2 3
1

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Capsular polysaccharides
Polysaccharides are very poor immunogens, largely because they rely on the
response of T-independent B cells and do not make good vaccines.
 To overcome this, effective vaccines contain polysaccharide that has been
chemically conjugated to a peptide antigen: tetanus toxoid is often used.
 T cells responding to the peptide then provide help for B cells responding to
the polysaccharide

DNA vaccine:
In this experimental approach, the gene for the
immunogenic protein is coated onto gold microspheres
and injected directly into cells (e.g., of the skin).
In mice, this has resulted in antibody production,
indicating that the genes were transcribed

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Ch1.Infections and Vaccines
 Ch1.Infections and Vaccines
Adjuvants
• Weaker antigens or subunits vaccines may be rendered more immunogenic by
the addition of other chemicals. Such chemicals are known as adjuvants.
• They provide the danger signal required for the innate immune system to
release signals to drive antibody and T-cell responses.
• Live vaccines generally do not require adjuvants because they are capable of
providing danger signals and stimulating Toll-like receptors (TLRs) themselves.

For example, bacille Calmette-

Guérin (BCG), the live vaccine
for tuberculosis, produces
large quantities of bacterial
sugars, which activate TLRs 2
and 4.
Killed whole vaccines also
contain substances that
activate TLRs and can act as
adjuvants.
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• Aluminum hydroxide (alum) is the only adjuvant licensed and
used routinely in human vaccines.
• It is used to boost the effects of a wide variety of subunit
vaccines.
• Aluminum hydroxide
 activates macrophages,
 which then secrete inflammatory cytokines
 and present antigen to T and B cells.
• Aluminum is not a powerful adjuvant
• Polynucleotide: Two new approaches are being used to
create improved adjuvants.
One in vaccine molecules, which activate TLRs.
These include molecules such as unmethylated cytosine and
guanine sequence (CpG) motifs that have been shown to improve
the antigenicity of several subunit vaccines.
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• Subunit vaccines do not enter the intracellular
antigen processing pathways so do not elicit
cytotoxic T cell (CTL) responses.

• CTL responses are particularly important in dealing

with intracellular infections such as HIV.

• Immunostimulatory complexes
(ISCOMs)  promotes CTL responses.
• ISCOMs are micelles of lipid and subunit antigen that
are lipophilic and able to penetrate cell membranes.
• ISCOMS have two special advantages over
conventional vaccines:
The antigen penetrates the cell membrane
 and is delivered to the antigen-presenting
pathways.
• SO stimulate T cells, including CTL.
• ISCOMs can be used for mucosal vaccines (e.g.,
through the nose) and induce widespread mucosal
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immunity in the gut and respiratory tract Ch1.Infections and Vaccines
 VACCINE SCHEDULES
• Vaccine schedules take into account the clinical implications
of each type of infection.
• For example, the main purpose of
rubella vaccine is to prevent
intrauterine infection (which can cause
birth deformities), so there is
little point in giving it before puberty.

• On the other hand, it would be desirable

to protect very young infants against Haemophilus,
because this organism causes most damage at this age
• However, even as conjugate vaccines, polysaccharides do
not elicit antibodies in newborn babies

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Ch1.Infections and Vaccines
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•Vaccine schedules also vary in different parts of the world
in the developing world, measles is a major cause of death in
infants and so the vaccine is given as early as possible.
In the developed world, measles has become rare and tends to
affect school age children, so the vaccine can be given slightly
later.

•The main factor affecting the use of vaccines in the developing world
is, however, cost.

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 Cancer Vaccines

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Ch1.Infections and Vaccines 20

 Cancer Vaccines
• To harness the body's defense system in the
fight against cancer
• What is a cancer vaccine?
• A composition which can stimulate the immune
system
– Normally against infectious diseases (ex. viruses)
– Antibodies
– Killer T-cells ***

• Killer T-cells are more effective against cancerous

cells
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 Therapeutic vs. Preventative
• Most vaccines are preventative:
– Given before the individual becomes
infected/acquires diseases
• Cancer vaccines are therapeutic
– Administered to individuals after they already
have cancer
– Goal- eliminate existing cancer cells
– One day we may be able to give preventative
vaccines….
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 Types of vaccines
• A cancer vaccine can be made:
– either of whole tumor cells
– substances contained by the tumor, called antigens
• whole cell vaccine
– tumor cells are taken out of the patient(s), and grown in
the laboratory
– tumor cells are treated
• They can no longer multiply
• There is nothing present that could infect the patient
• when whole tumor cells are injected into a person,
an immune response against the antigens on the
tumor cells is generated

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 Types of whole cell cancer vaccines
• An autologous whole cell vaccine is made with
your own whole, inactivated tumor cells

• An allogenic whole cell vaccine is made with

someone else’s whole, inactivated tumor cells
or several peoples' tumor cells combined

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 Antigen vaccines
• Made of whole cells, but of one or more
substances (called antigens) contained by the
tumor
– One tumor can have many antigens
– Some antigens are common to all cancers of a
particular type,
– and some antigens are unique to an individual
(a few antigens are shared between tumors of
different types of cancer)

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 Antigen delivery mechanisms
1. Proteins or pieces of protein from the tumor cells can be
given directly as the vaccine.

2. Genetic material coding for those proteins can be given (RNA or

DNA vaccine).

3. A virus can be enlisted to help deliver the antigen.

Viruses used in this way are called viral vectors,
and  do not make people sick or carry any diseases.
The virus is  capable of infecting only a small number of
human cells-- enough to start an immune response, but not
enough to make a person sick.

4. Viruses can also be engineered to make cytokines

or display proteins on their surface that 
help activate immune cells. These can be given
alone or with a vaccine to help the immune response.
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 Prospects for cancer vaccines
• Laboratory animals:
– When cancer vaccines are studied in laboratory
animals, cancer vaccines that stimulate the
immune system can cause tumors to withdraw
• In humans:
– Tumors have learned to escape the immune
system, and the immune system is not fighting
tumors effectively

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