Transcript Lecture 26. Prevention and Control -

Lecture 26. Prevention and
Control -- Vaccines
Flint et al., chapter 19, pp.
703 - 725
How do we acquire immunity?
Passive Immunity in Infants
Artificial Passive Immunity
• Gamma globulin
– Ig’s from pooled blood of at least 1,000
human donors
• variable content
• non-specific
• Specific immune globulin (SIG)
– higher titers of specific antibodies
• Antisera and antitoxins of animal origin
Antibody and effector T-cells are
the basis of protective immunity
•Primary infection stimulates an
initial immune response.
•A second infection is “inapparant”
because it provokes no symptoms.
•However, it does re-stimulate and
fine tune the immune response.
•Years later, memory B- and T-cells
can become reactivated upon
infection, protecting the individual
from disease
Artificial Active Immunity
• Vaccination (Immunization)
– exposing a person to material that is antigen
but NOT pathogenic.
History of Vaccination: Smallpox
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Smallpox killed or maimed 10% of humankind.
Killed > 300,000,000 people in the 20th century alone
Ancient Chinese history: a once in a lifetime disease.
11th century China and India: “Variolation”
– Scratch a healthy person with pus from infected person
– If they don’t die, they are immune for life
Vaccination
May 14, 1796, Edward Jenner
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Noted that milkmaids got cowpox, but not smallpox.
Injected pus from a cowpox lesion under the skin of a child
Waited 2 weeks
Deliberately infected the child with smallpox.
The boy survived
(Today, Jenner would be majorly sued, would lose his license,
be put on trial, get a good lawyer, write a book, and do the talk
show circuit…Just like Michael Jackson’s doctor!)
History of Vaccination
• Despite Jenner’s success, it
took 100 years til the next
vaccine.
• 1881, Louis Pasteur: coined
the word Vaccine.
– Used dried spinal cord from
rabid rabbit to create a rabies
vaccine.
– Also developed vaccines to
fowl cholera and anthrax
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July 6, 1885: 9 year old Joseph
Meister who was badly bitten by a
rabid dog.
Although Pasteur was not a
licensed physician and faced
legal risks, the boy would most
certainly have died without
treatment like many before him.
Pasteur decided to treat the boy
nevertheless and inoculated
Joseph with rabies vaccine that
had been tested only on dogs
previously.
The risk paid off and the boy
recovered dramatically.
Large scale vaccination programs
Fig. 19.1
• Dramatic improvements
in public health.
• Nobody in this room has
had…
– Smallpox, Polio, Measles,
Chickenpox
– Mumps, Rubella
• …Because of vaccination
• Smallpox is the only
human disease to ever
be eradicated
Characteristics of a good
vaccine
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Safe
Few side effects
Give long lasting, appropriate protection
Low in cost
Stable with long shelf life (no special storage
requirements)
• Easy to administer
• Inexpensive
• Public must see more benefit than risk
Types of vaccines
• whole agent
• subunit
– recombinant
– individual parts alone
Whole agent vaccines -- Killed
using heat or formaldehyde
Live virus
Killed virus
epitopes
epitopes
Inactivated polio vaccine (Salk)
Influenza (Classic)
Whole agent vaccines -Attenuated
• attenuated - a process that lessens the
virulence of a microbe
oral polio vaccine (Sabin),
MMR (measles, mumps, rubella)
TM
Influenza -- Flumist
Vaccines stimulate immune memory
•Killed virus vaccine requires
multiple doses (booster shots)
to adequately stimulate a
protective immune response
•Live virus vaccines replicate in
the host.
•No requirement for boosters.
Attenuation of viruses by passage
through non-human cells
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1. Pathogenic virus isolated
from patient, grown in
human cells
2. Infect monkey cells with
cultured virus
3. Virus acquires many
mutations that allow it to
grow well in monkey cells
4. Mutations make the virus
unable to grow well in
human cells
 Vaccine candidate
• Advantages for live vaccines
– multiply like natural organism
– require fewer doses and boosters
– long-lasting
• Disadvantages for live vaccines
– special storage
– back mutation
– side effects
Live attenuated Sabin oral poliovirus vaccine
Construction of recombinant attenuated virus
1. Isolate virus
2. Clone genome
3. Isolate virulence gene
4. Mutate or delete virulence
gene
5. Resulting virus is
• Viable
• Immunogenic
• Not virulent
• Can be used as a
vaccine
Subunit vaccines
• Single antigen or mixture
of antigens
• Safer (cannot reproduce)
• However, often less
effective than whole
agent vaccines
• Can be costly
• Always require boosters
Overcoming Subunit vaccine
problems
1. Multiple doses - booster shots
2. Use adjuvants
• prolongs stimulation of immune
response
• works by trapping the antigens in a
chemical complex and releases
them slowly
Vaccine delivery systems and adjuvants
ISCOMS as peptide delivery systems
Fig. 19.9
Recombinant vaccines
• Genetic
engineering
approach
• Hepatitis B
• Vaccina or
adenovirus
alteration
DNA vaccines
• Create a recombinant plasmid containing a
gene encoding a specific antigen.
• Engineer in sequences
1. Enabling it to be expressed in humans
2. Passaged through bacteria
• Introduce it into humans
• Let the human cells produce the antigen
• Present it to T-cells
• Provoke immune response
Representative results of DNA vaccine trials