Vaccines Flashcards
This lecture
What is a vaccine – and is it a drug?
The (very) basics of human immune
response
The known historical origins of inoculation
against smallpox
Cowpox as the first successful ‘vaccine’
The microbiology era – Pasteur and rabies
The polio vaccine
The measles vaccine
The toxoid vaccines – diphtheria and
tetanus
Australia’s current
childhood immunisation profile
What is a
vaccine – and is
it a drug?
Vaccines are biological preparations designed to
stimulate or ‘train’ the body’s immune response.
The idea is to get your body to fight and resist a
disease if you’re exposed to it.
The body is trained by the vaccine to recognise
particular pathogens (not normally found in the
body).
Vaccines are designed to prevent disease, rather
than treat it.
They can be considered drugs:
they are biological preparations (like hormone-based
drugs, eg. insulin)
they are prophylactic (like malaria medication)
BUT: they are not chemical-based (like
aspirin, nitroglycerin, chloroform).
By the end of this lecture, you will
be able to …
Describe the basic
processes of human
immune response
Identify key processes
and individuals involved
in the development of
inoculation and
vaccination.
Explain the difference
between vaccines and
antitoxins.
Describe variations in
Australia’s current
childhood immunisation
profile
What’s going
on inside you –
non-specific
immunity
The human immune system has two levels of
immunity:
non-specific immunity
specific immunity
Non-specific immunity is also called innate
immunity.
It’s how the human body protects itself against
foreign material perceived to be harmful (eg. viruses,
bacteria, parasites, splinters).
The skin and mucuous membranes are the first line
of defence.
Pathogens that breach these barriers will be
attacked by phagocytes.
These surround a pathogen, take it in, and neutralise
it.
What’s going
on inside you –
specific
immunity
Specific immunity works alongside non-specific
immunity.
It provides a targeted response against a specific
pathogen.
This kind of immunity only exists in vertebrates!
The specific immune response relies on white blood
cells (lymphocytes).
These are produced in bone marrow and become
different types of cells, including:
B cells
T cells
For example -
influenza
You get the flu from someone = the virus enters your body and
starts to replicate.
The flu virus produces an antigen which your body recognises
from an earlier bout of flu.
Specific “flu trained” T helper cells respond to this antigen by
stimulating B cells to produce lots of plasma cells.
These produce flu antibodies to combat the virus.
Helper T cells also switch on some killer T cells to surround and
destroy virus-infected cells in the body.
Once the flu is on the run, regulatory T cells calm everything
down again and switch off the immune response.
What’s going
on inside you –
B cells
B cells can mature and differentiate into plasma
cells that produce antibodies.
B cells alone are not good at making antibodies –
they rely on T cells to signal to them when it’s time
to produce them.
An antigen is a foreign material that triggers a
response from T and B cells.
When a B cell gets the message and recognises
the antigen it is coded to respond to, it produces lots
of plasma cells.
The plasma cells then secrete large numbers of
antibodies, which fight specific antigens circulating
in the blood.
The human body has B and T cells specific to
millions of different antigens.
Early 1700s – from
Turkey to the UK
Lady Mary Wortley Montagu, wife of a British
Ambassador, travelled in the Ottoman Empire in the early 1700s
In 1715, Lady Mary contracted smallpox and survived with
scarring (she lost her eyelashes).
She noticed that few people in the Turkish region had
smallpox scars and asked why – learned about inoculation.
Lady Mary had her son inoculated against smallpox in
Constantinople by Embassy surgeon Charles Maitland in 1718.
Later in England in 1721-22 she had her daughter inoculated as
well.
Inoculation
Pus was harvested from the lesions of a person
with active smallpox.
It was transferred to a cut on the back of the hand
or arm and bound up.
The inoculated person would develop a milder case
of smallpox, and thereafter be immune to it.
The origins of
inoculation
Smallpox (variola virus) – at least 10,000 years
old.
3 out of 10 infected people died, and survivors
were often facially scarred for life.
Survivors, however, became immune.
Early descriptions involve the use of live
smallpox to deliberately infect children
and adults.
Practice was called ‘inoculation’ and later
‘variolation’ (after the variola virus).
We don’t know the origins of this practice –
anecdotal evidence for northern Africa? The
area around Turkey? China?
Most written accounts of inoculation date reliably
from the very early 1700s and describe
practices from the 1600s.
Expansion of
inoculation in the UK
Lady Mary championed inoculation with the Royal Family.
Charles Maitland was granted permission to perform a
trial on six prisoners in London on 9 August 1721.
Several court physicians, members of the Royal Society, and
members of the College of Physicians observed the trial.
All prisoners survived and later proved to be immune.
Maitland successfully repeated the experiment on
orphaned children.
17 April 1722: Maitland successfully inoculated the two
daughters of the Princess of Wales.
Cowpox and smallpox
Trainee doctor Edward Jenner observed and was told that dairymaids
who had cowpox were immune from smallpox.
Jenner hypothesised that cowpox was protective but could also
be transmitted from one person to another, like variolation.
May 1796: Edward Jenner took pus from a cowpox lesion on Sarah
Nelms (dairymaid) and inoculated an 8-year-old boy, James Phipps.
Phipps developed mild fever, discomfort in the armpits, loss of appetite,
but on day 10 felt much better.
July 1796: Jenner inoculated Phipps again with fresh pus from a smallpox
lesion.
No disease developed, and Jenner concluded that the cowpox
inoculation had worked.
Instead of ‘variolation’, Jenner called this ‘vaccination’ (vacca = cow;
vaccinia = cowpox)
Spread of vaccination –
and opposition
1853; Smallpox vaccination becomes compulsory for babies
in the UK.
Some claimed vaccination were unsafe, or unnecessary.
Others argued that compulsory vaccination was
government interference in people’s lives.
1879:Anti Vaccination Society of America founded.
1890s: National Anti-Vaccination League (UK).
In the UK it became possible to opt out of vaccination
(Vaccination Act 1898).
Dame Mary
Gilmore (1865-
1962) - childhood
vaccination
experience in 1870s
Australia
All our … neighbours inoculated their children with
lymph from a calf, the family instrument being an
ordinary darning-needle. But I had to be ‘properly’
vaccinated. So I was taken to town to be done.
When my arm was bared, whichever of the medical
men it was crossed to the mantlepiece, on which
was a slide of glass covered with flies. The flies
rose in a cloud as he lifted it, and the horrible
surface, lymph and all, was spotted with
flyspecks.Though only a child, with horror I
thought, ‘Am I to be done with that?’ …
I remember days or weeks later on, opening my
eyes out of a stupor as I lay in bed, and seeing my
father and an old white ‘nurse’ standing beside me.
‘If she lives, she will lose her arm; it is black to the
shoulder now,’ the woman was saying. ‘But she
can’t live, she is too far gone.’
After the delirium passed I did live, but I lost all my
fingernails and toenails, and my hair fell out like
a long-dead person’s.About seven years old, I was
left absolutely bald, and for a year I had to wear a
cap or a hood to hide my bare skull.
Pasteur and
rabies
1879: Pasteur discovered by accident that
some bacterial cultures lost virulence
over time if they were left exposed to air
(attenuation).
First experiments used attenuated
anthrax (bacteria) on animals – successful
immunisation.
Pasteur experimented with rabies (virus)
which he attenuated by passing it through
a series of animals – successful
immunisation in dogs.
6 July 1885: Pasteur ‘vaccinated’ 9-yearold Joseph Meister, bitten by a rabid dog.
Meister received a total of 13 treatments
over 11 days and survived.
1886: Pasteur treated 350 people with
rabies vaccine with almost 100% success
rate.
Poliomyelitis
Humans are the only known species to carry this disease.
o Attacks motor neurons in the CNS.
o Highly infectious viral disease – children under 5 most at
risk.
o Paralysed US President Franklin Delano Roosevelt.
Around 19 out of every 20 people with poliovirus have no
symptoms = high risk of spreading.
Less than 1 in every 100 people will develop severe muscle
weakness.
In a small percentage of infections, can cause lifelong
paralysis or death.
1955 – Salk injectable polio vaccine approved for use in
the US.
1960 – Sabin oral polio vaccine approved for use in the
US.
Poliomyelitis
Australian 20th century epidemics: 1937-38, 1949 (Victoria), 1953
(NSW), 1961-62.
About four million Australians were infected in these epidemics (likely
under-reporting).
About 20,000 to 40,000 developed paralytic polio between 1930 and
1988.
Vaccination program began in Australia in 1956 (Salk vaccine).
Australia was declared officially polio-free in 2000 – but it is still a
notifiable disease.
Since 2014, poliovirus has only been found in Afghanistan and Pakistan.
Unvaccinated people may become infected if they travel to areas with
polio => may bring back polio to countries like Australia, where it could
affect unvaccinated people.
Diphtheria
antitoxin
Known in Europe since the 1600s; bacterium first identified in
1883.
Corynebacterium diphtheria releases a toxin that infects the
upper airways –> a membrane forms across the windpipe.
Can lead to suffocation and death; also CNS damage.
Children especially vulnerable.
Did not appear to attenuate – so how can we make
a vaccine?
Kitasato (1852-1931) and von Behring (1854-1917) successfully
produced a heat-treated toxin and treated guinea pigs with it.
Blood products from the guinea pigs contained an antitoxin
that worked to immunise against diphtheria.
Serum therapy or antitoxin therapy.
borrows antibodies made by another immune system that
will remain in the patient’s blood long enough to battle the
infection.
Measles
Highly contagious and dangerous virus (especially for
young children and pregnancy).
Ear infections occur in about 1 out of every 10 children
with measles.
Hospitalisation may be necessary.
Pneumonia. As many as 1 out of every 20 children with
measles gets pneumonia = common cause of death.
Blindness: corneal ulceration, keratitis.
Encephalitis. About 1 child out of every 1,000 who get
measles will develop encephalitis (swelling of the brain)
=> convulsions, deafness, cognitive impairments.
Death. Nearly 1 to 3 of every 1,000 children with
measles will die from respiratory and neurologic
complications.
Measles
vaccination
1954: measles outbreak at Boston
school = swabs and blood samples
taken.
Thomas Peebles MD successfully
cultured measles from samples
obtained from 11-year-old schoolboy
David Edmonston.
First vaccine developed by John
Enders from ‘Edmonston-B strain’ =
basis for US measles vaccines today.
Tested in the US 1958-1960
1961 = 100% effective and licensed
for public use in 1963.
Vaccine rolled out in Australia in
1969.
2014: Australia was declared
measles-free.
Variety of vaccine
platforms,
administration routes,
polyvalent vaccines
and improvements in
adjuvants and delivery
systems
MMR vaccine and autism
Global measles resurgence of 2018–2019
Lessons learnt
Future
directions in
vaccines
Future directions in vaccines
Future directions in vaccines
Future directions in vaccines
