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MII2 > 9. Vaccines > Flashcards

9. Vaccines Flashcards

1
Q

What is the story of vaccination discovery?

A

Modern day vaccination: Dr Eward Jenner (end of 18th century) - noticed that milkmaids didn’t catch smallpox as easily - inoculated a boy with cowpox - developed immunity against smallpox => full protection againts smallpox

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2
Q

When was smallpox officially eradicated?

A

1980

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3
Q

What are the earliest records of vaccination?

A
  • 7th century - Indian Budhists drank snake venom
  • 10th century variolation to prevent smallpox in China, India, Turkey
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4
Q

What is the chronological sequence of vaccine type development?

A
  • Bacterial vaccines
  • Viral vaccines
  • Molecular vaccines
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5
Q

What is passive immunisation?

A

Passive immunisation - transfer of serum antibodies - passive because the organism didn’t produce Ab itself

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6
Q

Who first developed passive immunisation?

A

Emil von Behring - Nobel prize in 1901 - developed passive immunisation for diphteria:

immunized guinea pigs against diphtheria with heat-treated blood products from animals recovered - antibodies to the diphtheria toxin - protected guinea pigs later exposed to lethal doses - next showed they could cure diphtheria in an animal by injecting it with the blood products of an immunized animal - Ab transfer

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7
Q

What are the modes of antibody transfer from immune to non-immune organism?

A

Passive immunity - Ab transfer:
1) Natural: transfer of mother’s Ab via placenta / mother milk (colostrum)

2) Artificial: Ab derived from blood of immune people / non-human immune animals

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8
Q

What is anti-sera?

A

Anti-sera / antisera / Ab serum - blood serum with antibodies against specific antigens, injected to treat or protect against specific diseases
- typically produced in donor animal (horse / sheep): animal immunised with non-lethal dose of antigen (toxin / venom / pathogen derived antigen) - blood from animal collected - Ab purified

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9
Q

What are the current aplications of Ab transfers?

A

Current Ab transfer applications:
- Rapid treatment: during acute ilness don’t need to wait for imm syst to develop
- Prevention measure: after transplantation

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10
Q

What are the adv and disadv of Ab transfer?

A

Ab transfer:
Adv:
- rapid acting
- support deficient immune system (beneficial to high-risk individuals)

Disadv:
- protection fades
- intravenous injection (instead of intramuscular)
- serum sickness - first time Ab recognised as Ag - imm response
- expensive / complicated to manufacture

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11
Q

What are monoclonal antibodies?

A

Monoclonal antibodies - A type of protein that is made in the laboratory and can bind to certain targets in the body - onse specific Ab for one Ag produced

Nobel prize 1984 Cesar Milsten, Georges J.F. Kohler

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12
Q

What was the initail method for monoclonal antibody production?

A
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13
Q

What are the major adv of monoclonal antibodies?

A

Adv of monoclonal antibodies:
- Single specificity (monoclonal)
- Unlimited supply (hybridomas can divide continously + can be frozen)
- Rare specificity Ab can be isolated
- Ab can be engineered - new specificieties, efficiencies
- more safe, less toxic in canceer threatment than chemotherapy

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14
Q

How are animal antibodies humanised?

A

Mouse monoclonal Ab can be recognised as Ag - use human Ab + adapt epitopes for Ag - add complementarity determining region (CDR) produced by mouse cells for the specific Ag (won’t be recognised as Ag) - Ag bound by the engineered Ab but not recognised as foreign because human Ab core is used

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15
Q

What are the currently used methods for monoclonal antibody production?

A
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16
Q

What do therapeutic monoclonal antibodies target?

A
  • Cytokines
  • Growth factor receptors
  • Check point inhibitors
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17
Q

What are the main principles in vaccination?

A
  • Introduce imm syst to a pathogen in a controlled env
  • Cause imm syst to remember pathogen and respond to it
  • Enable imm syst to effectively clear the pathogen to prevent disease
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18
Q

What are the characteristics sought in vaccines?

A
  • long lasting immunity
  • safe
  • stable
  • easy to store and administer
  • single dose
  • affordable
  • pathogen evolution-proof
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19
Q

What are the features of adaptive immune system?

A
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20
Q

What are the main immune system components used in vaccination?

A
  • Ab / B cells
  • CD4 T cells
  • CD8 T cells
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21
Q

What are the developed vaccines for polio?

A

Different types of vaccined developed for polio:
- Inactivated (whole pathogen killed): inactivated by formalin Jonas Salk
- Live-attenuated (weakened pathogen form): Albert Sabin

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22
Q

How are chicken eggs used for vaccine production?

A

Chicken eggs - vertebrate hosts for viral replication - different viruses grow in different egg parts - difficult host because need skilled professional to precisely inject the virus into a specific part + conditions for storage

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23
Q

What are the limitations of traditional vaccine production methods?

A
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24
Q

What are sub-unit vaccines?

A

Not entire organism - use components - ex proteins

Adv: no extra pathogenic particles (ex DNA)
Disadv: proteins may differ when outside the organism; production expensive

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25
Q

What is a vector vaccine?

A

Vector vaccine - vaccine which uses a vector (ex virus) to deliver genetic material to be transcribed as mRNA in host cells to produce necessary molecules

26
Q

What are the common examples of viral and bacterial vaccines?

A

Viral: influenza, polio, smallpox

Bacterial: meningitis, pneumonia, tuberculosis

27
Q

What are VLPs?

A

Virus like particles (VLP) - mimic viruses but are not infectious - more safe to administer

  • Non-enveloped VLPs - composed of 1+ viral structural proteins
  • Enveloped VLPs consist of host cell membrane with viral proteins on outer surface
28
Q

What are the types of vaccines types based on vector type?

A
29
Q

What is the structure of outer membrane vesicle vaccine technology?

A
30
Q

What is the structure of protein-polysaccharide conjugate vaccine technology?

A
31
Q

What are the vaccine delivery routes?

A
32
Q

Explain what is FluMist

A
33
Q

What are vaccine adjuvants and why are they necessary?

A

Vaccine adjuvants - ingredient in vaccines - helps create a stronger immune response after the vaccine delivery

Essential for enhancing + directing adaptive imm response to vaccine Ag - response mediated by B and T cells

34
Q

What are the main advantages of using an adjuvant?

A
35
Q

Explain the sequence of events after immunisation with a vaccine containing AS01 chemical

A

AS01 - adjuvant

36
Q

What is the role of DC in vaccination?

A

DCs interact with B and T cells to launch a specific, adaptive immune response to the pathogen

37
Q

What are the specific roles of an adjuvant?

A
  • extend presence of Ag
  • locally activate macrophages and lymphocytes
  • cupport local production of cytokines
  • activate APCs, support migration and absorption, present Ag
38
Q

What is the mechanism of action of an adjuvant?

A

Mimic microbe components which bind to PRRs on APCs

39
Q

What are the benefits and risks of a vaccine adjuvant?

A
40
Q

What are the disadvantages of live-attenuated vaccines compared to inactivated?

A

Live-attenuated can mutate - revertant mutants - don’t help to clear but spread the infection

41
Q

How it is decided what type of polio vaccine to be approved in a country?

A

Depends on polop levels in the country - if eradicated or not

42
Q

What are the advantages and risks of live-attenuated vaccines?

A
43
Q

Define what is an antigenic drift?

A

Antigenic drift - viral genetic variation from mutation accumulation in the virus genes coding for virus-surface proteins that host antibodies recognize

44
Q

What is the challenge of antigenic drift?

A

Antigenic drift -> person susceptible to same virus infection again - because antigenic drift has changed the virus’ antigenic properties enough that a person’s existing Ab won’t effectively recognize and neutralize the antigenically different flu viruses

45
Q

What is the universal flu vaccine?

A

Universal flu vaccine - flu vaccine effective against all influenza strains regardless of the virus sub type, antigenic drift or antigenic shift.

46
Q

How is the univeral flu vaccine created?

A

Vaccine includes mRNAs for a key virus protein called hemagglutinin (HA) from all 20 influenza types

47
Q

What are the steps in vaccine development?

A
48
Q

What are the steps in vaccine development?

A
49
Q

What are the coronaviruses that have emerged?

A
  • SARS-CoV (Nov 2002) - didn’t spread into a global problem
  • MERS-CoV (Jan 2012) - didn’t spread much beyond the middle east
  • SARS-CoV2 (2019) - global pandemic
50
Q

Why was SARS-CoV2 good at spreading?

A
  • respiratory virus but can infect many tissues
  • trnasmitted before symptoms appear
51
Q

What is the infection mechanism of SARS-CoV2?

A

Surface spike glycoprotein - binds to angiotensin - converts enzyme 2 receptor (on many mammalian cells)

Spike protein - Ag of interest in vaccine

52
Q

What are the tools used to battle COVID-19?

A
  • Anti-virals
  • Monoclonal antibodies (against spiek proteins)
  • Corticosteroids (supress hyperimmune response)
  • Vaccines (preventative)
53
Q

Why was COVID19 vaccines developed so quickly?

A
  • more efficient technology/methods
  • years of advanced research
  • Phase II and III trials performed simultaneously
  • a few steps skipped
  • supercharged funding
54
Q

What are the existing vaccine strategies? What are the specific COVID-19 vaccines using those strategies?

A
55
Q

Explain Sinopharm vaccine

A

Sinopharm:
- inactivated SARS-CoV2

56
Q

Explain Oxford-AstraZeneca vaccine

A

Oxford-AstraZeneca:
- virus vectored - ChAdOx1 - chimpanzee adenovirus

57
Q

Explain Gamaleya (Sputnik V) vaccine

A

Gamaleya (Sputnik V) - virus vectored - identical strategy to Oxford-AstraZeneca - only a combination of 2 adenoviruses used

58
Q

Explain Pfizer-BioNTech vaccine

A

Pfizer-BioNTech: mRNA (no additional adjuvant - nanoparticle surface acts as an adjuvant) - mRNA codes for a modified S protein - 2 am a substitutions compared to WT

59
Q

Explain Moderna vaccine

A

Moderna: mRNA (same as Pfizer-BioNTech just the nanoparticle a bit different + higher Ag dose)

60
Q

Explain EpiVacCorona and Novavax vaccines

A

EpiVacCorona (Russian - little info) / Novavax: protein subunit

61
Q

What are the challenges related to effective vaccine administration across the world?

A

MII2 (9 decks)

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