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2052 DYLAN > vaccines > Flashcards

vaccines Flashcards

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

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2
Q

Outcomes of vaccines

A
  • prevention of disease and transmission
    • Eradication
    • Potentially treating non-infectious disease
      ○ Cancer, Alzheimers etc.
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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

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13
Q

Killed/inactivated

A

Parenteral (inject)

Multiple dose

Adjuvant required

safe

Heat stable

High cost

Short/ long duration of immunity

Mainly IgG

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14
Q

Live attenuate - BCG

A

○ Bovine TB strain passaged in vitro
○ No reversion
Administer intradermally

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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

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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)
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
25
Q

Recombinant antigen vaccine - Hep B example

A

○ 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
Q

Protein subunits

A 
○ 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
Q

VLPs

A

○ 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
Q

H65 for TB

A

○ Looked at proteins transcribed during infection
○ Looked at immune response
Found 6 immunogenic proteins put into a single fusion protein named H65

29
Q

Single peptide vaccines

A
  • 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
Q

Adjuvants

A
  • 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
Q

Recombinant vector vaccines

A

Insertion of foreign genes into a live viral vector

32
Q

Multivalent attenuated viral vectors

A

○ Adenovirus
○ Attenuated measles virus
Canary pox virus

33
Q

Bacterial vector e.g. AstraZeneca covid 19

A

○ 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
Q

Nucleic acid vaccine

A
  • 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
Q

DNA nucleid acid vaccine

A
  • 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
Q

Edible vaccine

A
  • 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
Q

Sometimes vaccine fails

A
  • Wrong immune response
    • Response too low
    • Wrong target
    • Immature immune system
    • Non-responders
    • Immunosuppression
    • Immune evasion
      Antigenic variation
38
Q

Side effects

A
  • Swelling
    • Allergic response (grown in eggs and yeast)
    • Seizures
    • Guillian-barre syndrome
      ○ Triggers auto-immunity
    • Harmful effects on foetus and immunocompromised

2052 DYLAN (12 decks)

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