vaccines Flashcards
(38 cards)
1
Q
History
A
Ancient Egyptians, Indians and Chinese 1100BC discovered
1796 Jenner develops small pox vaccine
- Observed milkmaids who contracted cow pox did not get small pox
- Scratched a boy with needle with fluid of cow pox infection
- The boy was later exposed to small pox but was resistant
1885 Pasteur rabies vaccine
1979 smallpox eradicated
- Cowpox and small pox shared similar antigens
- Immunisation with cow pox induced antibodies against cow pox
Cow pox antibodies neutralised the smallpox virus
2
Q
Outcomes of vaccines
A
- prevention of disease and transmission
- Eradication
- Potentially treating non-infectious disease
○ Cancer, Alzheimers etc.
3
Q
Eradication successful for smallpox
A
- Disease limited to humans (cant exist in any other animal or soil etc.)
- No long term carriers (no asymptomatic)
- Always recognisable
- Few variants/serotypes
- Stable, cheap, effective vaccine
- Eradication is cost effective
Global surveillance
4
Q
Polio eradication program
A
- Highly infectious Faecal oral route disease
- Mostly under 5yr old children
- Invades intestine and nervous system
- Paralysis in limbs or in some cases breathing muscles (death)
- Inactivated (salk) vaccine 1955 (IPV)
○ Took 3 strains grown in monkey kidney cells –> formalin treated to inactivated virus - Attenuated (oral, Sabin) vaccine 1962 (OPV)
○ 3 polio strains passaged to accumulate mutations
§ Strain 1 - 57 mutations
§ Strain 2 - 2 mutations
Strain 3 - 10 mutations
5
Q
cVDPV
A
- Circulating vaccine-derived polio virus
If OPV vaccinated children shed virus in an under immunized population there is a chance for infection of immunocompromised and reversion to virulence
6
Q
Measles
A
- R0 =18
- Many deaths from pneumonia
- If contracted before age 2 - increase risk of rare complications, SSPE
- 1980 –> 2016 - 2.6m/yr deaths –> 90,000/yr
- In USA example
○ 1963-1983 - 400,000 cases –> 1479 cases with vaccine
○ 1990 - only 70% coverage –> cases rise to 27,786
○ 1993 - public health effort cause immunisation to 90% range - 312 cases
○ 2000 - USA declared effectively eradicated with case load of <60 cases/yr
2014 - measles cases increase due to lack of vaccination
7
Q
TB
A
- Incredibly difficult to treat, many antibiotics
- No sufficient treatment yet
- Anyone with TB needs to be treated
○ Cost high - Focus on prevention
Drastically lower cost
8
Q
Types of immunisation - passive
A
- Transfer of immunity to patient by using specific antibodies = immune prophylaxis
- You get given it (antibodies) not make it yourself
- Best given before infection
- Rapid onset of protection
- Maternal immunity - antibodies from mother to infant via placenta or breast milk
- Limited duration 3-6 months
○ Antitoxins, tetanus
Gas gangrene, Hep A, measles
9
Q
Types of immunisation - active
A
- Induction of a specific, protective immune response by exposure to antigen = vaccination
- Introduce immune system to a safe form of a micro-organism that will induce immune response
When infection occurs, a secondary response will occur- more rapidly and greater magnitude
- Introduce immune system to a safe form of a micro-organism that will induce immune response
10
Q
Ideal vaccine
A
- Safe (minimal side-effects)
- Produce a protective immune response
- Long lasting response (memory)
- Stable (effective after storage and shipping, cold chain
- Single dose
- Oral/inhaled administration
Low cost (measles vaccination = 1 USD)
11
Q
Vaccine types
A
- Live attenuated
- Killed/inactivated
- Vaccine must contain at least 1 component of the organism
The more components, the more the immune response will resemble that against the target organism
12
Q
Live attenuated
A
oral
Single dose
No adjuvant
Possible reversion to virulence
Requires cold chain
Low cost
Long duration of immunity
IgG, IgA, cell mediated
13
Q
Killed/inactivated
A
Parenteral (inject)
Multiple dose
Adjuvant required
safe
Heat stable
High cost
Short/ long duration of immunity
Mainly IgG
14
Q
Live attenuate - BCG
A
○ Bovine TB strain passaged in vitro
○ No reversion
Administer intradermally
15
Q
Live attenuated - Oral polio virus
A
○ Passaged in monkey kidney cells
○ Rare reversion
○ Good mucosal immunity
Potential to cause vaccine derived polio in immunocompromised
16
Q
Live attenuated - bacterial vaccine
A
○ Typhoid
§ Oral for travellers to areas where typhoid is prevalent
○ TB
BCG used for people at special risk of contraction
17
Q
Live attenuated- viral vaccine
A
○ Chicken pox ○ Measles ○ Mumps ○ Rubella ○ Poliomyelitis ○ Yellow fever ○ Rotavirus
18
Q
Killed/inactivated vaccines -
A
- derived treatment with chemicals
- Non-infectious, safe
- Less immunogenic and require adjuvants
- Polio
○ Inactivated with formaldehyde (adjuvant) - Influenza
○ Same as polio but cultured in eggs - Hep A
○ Same as polio - Typhoid
○ Killed whole cells - Cholera
○ Killed whole cells - Covid 19
○ Grown in Vero cells
○ Inactivated with BPL
Adjuvant added
19
Q
Classical vaccinology
A
Growing pathogens
20
Q
Reverse vaccinology
A
- Design from information
E.g. Finding particular antigens and direct antibodies to those
21
Q
Subunit vaccines - “acellular”
A
- Used when immunity depends on antibody to a particular microbial component that can be purified
- Can be a protein e.g. toxoid (inactivate)
- Or polysaccharide e.g. capsules (e.g. Neisseria meningitidis)
Non-infectious viral-like particles such as HPV
22
Q
Toxoids
A
- When a disease is caused by a toxin, immunity may depend not on Ab to the microbe, but on Ab to the toxin (anti-toxin)
- Inactivated bacterial toxin (formaldehyde)
○ DTaP (triple antigen) vaccine
Tdap (booster)
- Inactivated bacterial toxin (formaldehyde)
23
Q
Conjugant vaccines
A
- Purified capsular material can be a good target
- But often not very immunogenic
- Conjugating linking a less immunogenic Ag to a strong protein Ag(toxoid) increases recognition of the vaccine antigen
Whooping cough - Pertussis toxoid
Influenza - Capsule
Strep - Capsule
Neisseria meningitidis - Capsule
Typhoid
Capsule
24
Q
Recombinant antigen vaccine
A
- Where protective antigen is known, can be produced by recombinant DNA tech
- Useful in cases where the causative agent cannot be grown in vitro
○ Rabies - G antigen
○ Influenza - recombinant hemagglutinin
○ Hep B - surface antigen
Covid 19 - recombinant spike protein
- Useful in cases where the causative agent cannot be grown in vitro
25
Recombinant antigen vaccine - Hep B example
○ Gene encoding hep b surface antigen (HBSAg) cloned in yeast plasmid
○ The yeast produce surface hep b surface antigen to be purified
○ Move to
Block binding to cell
26
Protein subunits
```
○ Identify protein required for protective immunity
○ Clone gene encoding protein
○ Express and purify
○ Add adjuvant
○ No need to grow virus
Very safe to scale up
```
27
VLPs
○ Virus like particle
○ Look like virus to host no genetic material
○ No infection
○ Display antigen
○ insert gene and surface protein into vector in eukaryotic, yeast of insect cell
Self-assembly with similar surface proteins
28
H65 for TB
○ Looked at proteins transcribed during infection
○ Looked at immune response
Found 6 immunogenic proteins put into a single fusion protein named H65
29
Single peptide vaccines
- Only use epitope needed to stimulate immune response
○ Identify sequence and chemically synthesize the short peptide
- Get epitope required for protective immunity from immune host
○ Take b cells and clone to find the antibody
○ Take the neutralising antibody
○ Look at the shape of the binding site for the antibody
Mimic the molecule at the binding site
30
Adjuvants
- Soluble antigens are less immunogenic than particulate antigens
○ So, most single proteins or toxoids require an adjuvant
- Adjuvants enhance immune response
○ Local inflammation
○ Depot slow release of antigen
Modern adjuvants to enhance and direct the desired type of immune response
31
Recombinant vector vaccines
Insertion of foreign genes into a live viral vector
32
Multivalent attenuated viral vectors
○ Adenovirus
○ Attenuated measles virus
Canary pox virus
33
Bacterial vector e.g. AstraZeneca covid 19
○ If we know the antigen that needs to be expressed
○ We can clone that gene
○ Transform that into a bacterial vector
○ Once in a bacteria the antigen is expressed
§ Floating in cytoplasm
§ On surface
○ Multivalent attenuated bacterial vectors
§ Attenuated salmonella typhi
□ Oral
□ Antigens for enteric pathogens
§ Attenuated s. enterica serovar typhimurium
□ Oral
Express recombinant PSA antigen of prostate cancer
34
Nucleic acid vaccine
- Just DNA or just RNA as vaccine
- Cheap, easy
- Pfizer covid 19 vaccine
- DNA
○ DNA that contains gene of interest
§ Creates pores in membrane that increase uptake of DNA into cell that allows gene to be expressed in the cell
- RNA
○ mRNA encased in lipid coat so it can enter cell and express the gene
§ Lipid fuses with cell membrane and allows mRNA to enter cytoplasm to make viral protein to be taken up by immune system
○ Not as stable as DNA
§ Storage at -70 degrees
Self adjuvating (induce inflammation)
35
DNA nucleid acid vaccine
- put into a plasmid that has a promotor that switches on only in human cells
○ Either a syringe or gene gun
○ Once in nucleus will transcribe mRNA and trick cell to make antigen
§ Either send out of cell as free antigen
§ Or get broken up as a peptide and get presented on MHC class 1
- Injection of naked DNA comprising of foreign gene and a plasmid
- Plasmid must be able to replicate in bacteria and eukaryotic cells
Foreign gene under control of eukaryotic promotor (e.g. cytomegalovirus)
36
Edible vaccine
- Potential to feed people helicobacter pylori a gut bacteria that express vaccine antigens
- Expression of vaccine antigens in genetically engineered plants
- Nanopatches
○ Needle free
○ Dry coat stamp
○ No adjuvants
○ No refrigeration
○ Cheap
No reduction in dose
37
Sometimes vaccine fails
- Wrong immune response
- Response too low
- Wrong target
- Immature immune system
- Non-responders
- Immunosuppression
- Immune evasion
Antigenic variation
38
Side effects
- Swelling
- Allergic response (grown in eggs and yeast)
- Seizures
- Guillian-barre syndrome
○ Triggers auto-immunity
- Harmful effects on foetus and immunocompromised
