Immunization

SPT1203 Dr. N. D. Soko

Remember
these guys…..
Variolation
(18th Century)
• Earliest record Wan Quan’s
Douzhen Xinfa (1499-1582)
• Derived from a unique
infection agent : variola virus
• Principle: to cause mild
infection with an unmodified
pathogen
• Immunity to smallpox was
conferred by inserting dried
exudate of smallpox into the
nose
 Edward Jenner -
1796
• Steps
• Collected the cowpox virus from
the lesions of a milkmaid
• Inoculated 8 year old James Phipps
with the virus
• James developed fever and rash
but recovered after a few weeks
• Inoculated James Phipps with
smallpox virus upon recovery
• What do you think happened?
Louis Pastuer
• Anthrax vaccine
1. 24 sheep, 1 goat, 6 cows inoculated
twice with attenuated anthrax bacillus
✓ 5 May 1881
✓ 17 May 1881
2. Control group unvaccinated
3. 31 May 1881
✓ All animals inoculated with virulent anthrax
bacilli
4. 2 June 1881
✓ All vaccinated animals alive
✓ All unvaccinated animals all dead
Immunization
• A process by which resistance is
acquired
• It may even occur unintentionally
when exposed unknowingly
• It occurs via Abs
• Its main aim is to prevent illness or
complications that arise due to
illness
• Immunization is the process by
which immunity is conferred
 Immunization

• Can be passive or active

• Passive immunization : injection or acquisition
of Abs or serum with Abs from another
individual’s immune system
• Short lasting immunity
• Acquired immunization: individual’s own
immune system is stimulated to actively produce
their own Abs
• Long lasting immunity
 • Imparts immediate but short lived immunity
• May occur naturally or artificially
• Examples of natural passive immunisation
include:
• Fetus receives Abs from mother across the
Passive placenta
• Breastfeeding infant ingests Abs from its
immunisation mother’s milk
• examples of artificial passive immunisation
include
• Injection with immune serum globulin
containing artificial Abs
 Active immunisation

• Stimulates the immune system to produce Abs

• Can occur naturally due to exposure to Ag
• And artificially through vaccination
• Vaccines =preparations containing Ags that stimulate an immune response
• Renders immunity without causing disease
• Renders long lasting immunity
Immunization
• Gives the body opportunity to
be prepared even before
exposure to pathogen
• This preparation renders
immunity without ass
consequences of illness caused
by natural infection
Vaccination
Vaccines “Vaccine: A preparation that is used to stimulate the
body’s immune response against diseases. Vaccines are
usually administered through needle injections, but
some can be administered by mouth or sprayed into
• Commonly termed an injection!!! the nose.”…..CDC
• Or the grim ripper!!
 “ a biological product manufactured from
a whole bacterium or virus, its
constituents (proteins or polysaccharides)
or its products (toxins) from which the
Vaccines capacity to produce the disease is
destroyed by various means, while the
capacity to induce an immune response
(immunogenicity) is preserved.”
 a preparation that is administered to stimulate the
body’s immune response against a specific
infectious agent
• Attenuated oral polio vaccine
• A tetanus toxoid-containing vaccine

A preparation or immunotherapy that is used to

stimulate the body’s immune response against
noninfectious substances, agents or disease
Vaccines • Use of dendritic cells to train the immune system to recognise
tumour cells

A preparation of genetic material that is used by the

cells of the body to produce an antigenic substance

• E.g., Moderna coronavirus vaccine

• Contains spike protein mRNA
• Host cells express spike protein triggering an immune response
Vaccine constituents
• A vaccine has numerous constituents
• This differ per vaccine
• But each serve a unique purpose
• E.g.
✓Provide immunity
✓Keep the vaccine safe
✓Extend vaccine shelf life
✓Production of the actual vaccine
 Vaccine constituents

• The active ingredient

• Also called the active ingredient/Ag
• solicits immune response
• Specific to the target disease
• Strong enough to solicit immune response
• But weak enough to not cause disease
Vaccine constituents
2. Adjuvants
• E.g. aluminium salts
• These are added to enhance the body’s immune response
• Adjuvants are not added to every vaccine
• Prolong presence of Ag @ site of inoculation
• Allows vaccine to released gradually into the blood
• Promotes activation of APCs
• Thus immune response is also longer
• To avoid inflammation, they are injected intramuscularly
 Vaccine constituents
3. Stabilisers
• are added to keep the vaccine stable and maintain efficacy
• Some prevent vaccine components from sticking to the storage vessel
• Most stabilisers are found naturally in the body
• They therefore pose no known risks
• Stabilisers include bovine albumin, bovine serum, human serum
albumin, gelatin, glycine, lactose, sorbitol, sucrose, saccharose
• Polysorbate 20 and 80 (Tween 20 or 80) are used as surfactants to make
the product homogenous
Vaccine constituents
4. Preservatives
• Used to preserve the vaccine
• Prevents microbial contamination
• Particularly useful for multi-dose vaccines
• Use of mecury based thiomersal marred in controversy
• Associated with increased autism with MMR vaccine
• No evidence to this effect
• But treduced uptake of childhood vaccines
• Phenol and phenoxyethanol commonly used as preservatives
 Vaccine constituents
5. Trace components
• These are part of the manufacturing process that are residual in the
vaccine
• Vaccines are grown in different culture media
• E.g. bovine proteins, chick embryo cells, embryonated chicken eggs,
human diploid cells & yeasts
• Egg protein is sometimes observed as a residual trace component
• Another example is formaldehyde
• Formaldehyde is used during manufacturing to kill viruses and kill toxins
Vaccine constituents

6. Antibiotics 7. Diluent
• Used in the manufacture of • Also called suspending fluid
vaccines to suppress microbial • Used to dilute vaccine to
growth required concentration
• Exist in the vaccine as a trace • Water and saline water most
component common
• Penicillin causes allergic reaction • Sometimes complex proteins are
and is often not used also used
• Neomycin & gentamycin are
commonly used
Types of vaccines
Types of vaccines
• 1st vaccine was against small pox
• Weakened cowpox virus was used
• Cowpox virus is similar to small pox virus
• Elicited a weaker disease
• Rabies was the first virus attenuated in a lab
• Vaccines are now made in numerous ways:
✓Live attenuated virus
✓Inactivated/killed organisms
✓Inactivated toxins
✓Segments of the pathogen
Whole microbe approach
• Is the traditional method
• Immunogen is typically the whole organism
• Elicits a very strong immune response
• Most vaccines are based on this approach
• 3 main groups:
i. Inactivated vaccine
ii. Live-attenuated vaccine
iii. Viral vector vaccine
Inactivated vaccine
• Virulent pathogen is killed or inactivated
• Chemicals, heat or irradiation are used
• Chemicals employed include formalin or formaldehyde
• Inactivation destroys pathogens ability to replicate
• Also destroys ability to revert to virulence
• However pathogen is intact to elicit response
• Requires biosafety level > 3
• Takes time to produce due to culturing
• Immune response is not strong hence boosters are often required
• E.g. polio (IPV), hepatitis A, rabies & influenza vaccines
Live attenuated vaccines
• Immunogen is a weakened version of the pathogen
• It therefore is less virulent & causes less serious illness
• Very close to natural infection
• Hence immune response is often effective and long lasting
• Most are viral
• E.g. measles, mumps, rubella (MMR), varicella (chicken pox), yellow
fever and typhoid
• Should not be administered to immunocompromised individuals
Live attenuated vaccine
• Viral culture done in animal
embryos
• Viral cultured under conditions
that deactivate their virulent
properties
• Virus is passed through till it
loses virulence in humans
• A single virus can be passed
through 200 chick embryos
Viral vector vaccine
• Uses a safe viral vector to deliver the
immunogen
• Immunogen is often a specific sub
part of the pathogen
• Under whole microbe approach as a
whole viral vector is used
• Genetic engineering joins gene for
immunogen with viral vector DNA
• Safe virus is then introduced into the
host
• Who in turn makes the immunogen
• Immune response is elicited
• E.g. Ebola virus & coronavirus
Toxoids
• Some bacteria do not themselves cause illness
• However they secrete toxins that cause illness
• E.g. Clostridium tetani produces a neurotoxin called tetanospasmin
• Vaccines of such bacteria contain inactivated toxin
• Toxoids = vaccines where immunogen is an inactivated toxin
• Another e.g. of a toxoid is the diphtheria vaccine
• Crotalus atox is a rattlesnake toxoid vaccine
2.0 Subunit approach
• Contains only pieces of the pathogen
• Done by isolating a specific subunit of the pathogen and presenting it
as an agent
• Some subunits are via genetic engineering
• Subunits minimise side effects
• Most childhood vaccines are subunit vaccines
• E.g. whooping cough, tetanus, diphtheria, meningococcal meningitis
and Hepatitis B
2.0 Subunit approach
• Polysaccharide vaccines can be designed for infections where
pathogen sugars cause infection
• E.g. Haemophilus influenzae (HiB) polysac vaccine
• Virus based rDNA is another way of creating subunits
• E.g. virus-like particle vaccines against HPV
• Nanoparticle vaccines are still under trial
• E.g. ferretin nanoparticles against influenza
Genetic approach
3.0 Genetic Approach
• Involve introducing genetic material encoding the immunogen
• The body’s own cell machinery then expresses this gene
• Relatively new way of developing vaccines
• Unlicensed before the onset of Covid-19
• Potential advantages of this approach include:
✓Stimulation of long term immunity
✓Improved vaccine stability
✓Relative ease of large scale manufacture
DNA Vaccine
• Are plasmid DNA carrying genes
encoding the immunogen
• Mechanism involves insertion
and expression of viral/bacterial
DNA in human cells
• Examples include:
i. SARS-CoV-2
ii. H5N1 avian influenza
iii. H1N1 pandemic influenza
iv. Zika virus
mRNA Vaccine

• mRNA is packaged
into a vector such as
lipid nanoparticles
• mRNA is inserted
into individual
• mRNA translated
into immunogen
Covid vaccines
Stages in vaccine development

https://www.ncbi.nlm.nih.gov/books/NBK236428/