Download Intorduction to basic vaccine technology - UK-CAB

Phagocyte
B cells
B Cell
Receptor
Naïve B cell
B cells and antibodies
B cell attaches to
antigen cloning of
daughter cells
daughter cells
produce
antibodies
Antibodies
neutralise
antibodies
phagocyte
consumes
an antibody
coated virus
Cytotoxic CD8 cells
CD8 cells can recognise
markers on the outside
of infected cells
CD8 destroys infected
cell which stops cell from
producing more virus or bacteria
Antigen presenting cells
These cells
can engulf
invading
organisms
Antigens
presented
to CD4
cells
The foreign organism is broken
up into smaller pieces
CD4 cell
Analogy for the immune system
Naïve and Memory B cells

Naïve B cell
Once activated it divides many times
making two types of clones
 The plasma cell which makes and releases
large amounts of the appropriate antibody
 The memory B cell which can live for years
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Memory B cells

The existence of memory B cells means
that the body can respond much more
quickly
CD4 and CD8

Cluster of Differentiation
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CD4 cells
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Th1 (humoral response) Th2 (cell mediated
response) Th0 (??)
CD8 cells
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Molecules on the surface of the cells that help the
T cell attach to the antigen
Cytotoxic lymphocytes (CTL)
CD45RA – Naïve cells
CD45RO – Memory cells
CD4 count viral load over time
Levels in the Blood
Viral Load
CD4 Count
Set Point
Below the limit of the test
Seroconversion
Asymptomatic
Symptomatic
HIV virion
Fatty
(lipid bilayer)
membrane
Glycoprotein
gp120
Protein p18
Protein p24
Reverse
transcriptase
enzyme
Vaccine - Ideal characteristics
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Prevent transmission by mucosa &
injecting
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
Immune system responses

Humoral response

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Cell-mediated response
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Based on cytotoxic CD8 cells
Mucosal immunity


Based on antibodies and the B cells that produce
them
The above but concentrated in the mucosal
membranes where most transmission occurs
Current trend

is to aim to stimulate a sufficient HIV-specific CTL
response to control or prevent HIV infection
Types of vaccine

Live attenuated vaccines
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Defective or weakened form of the virus
Previous example original smallpox vaccine,
vaccinia
Research in monkeys indicates may slowly lead to
immune disease
Inactivated or 'killed' vaccines
Recombinant sub-unit envelope vaccines
Recombinant vectored vaccines
DNA vaccines and replicons
Combination vaccines or ‘prime and boost’
Types of vaccine

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Live attenuated vaccines
Inactivated or 'killed' vaccines
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Second classic technique (e.g. Dr Jonas Salk in
creating the world's first successful polio vaccine)
No-one has yet claimed any significant success
Maybe difficult to distinguish between vaccine
immune response and infection
Recombinant sub-unit envelope vaccines
Recombinant vectored vaccines
DNA vaccines and replicons
Combination vaccines or ‘prime and boost’
Types of vaccine



Live attenuated vaccines
Inactivated or 'killed' vaccines
Recombinant sub-unit envelope vaccines

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Seek to stimulate antibodies to HIV by mimicking
proteins on the surface of HIV (e.g. gp120)
Initial research was strain-specific and produced
poor antibody responses
Recently more hope
Recombinant vectored vaccines
DNA vaccines and replicons
Combination vaccines or ‘prime and boost’
Types of vaccine

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Live attenuated vaccines
Inactivated or 'killed' vaccines
Recombinant sub-unit envelope vaccines
Recombinant vectored vaccines

incorporate harmless bits of HIV into established
vaccines
• ALVAC series of vaccines are canarypox based vaccines
• Vaccine strains of adenovirus
• recombinant rabies virus vaccines
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DNA vaccines and replicons
Combination vaccines or ‘prime and boost’
Types of vaccine





Live attenuated vaccines
Inactivated or 'killed' vaccines
Recombinant sub-unit envelope vaccines
Recombinant vectored vaccines
DNA vaccines and replicons
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
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involve HIV genetic sequences which, once
injected, induce expression of HIV antigens by
human cells.
In the case of replicons, these sequences are
wrapped in the outer coat of an unrelated virus.
Combination vaccines or ‘prime and boost’