Chapter 6 Evolution of Adjuvants Across the Centuries Flashcards

1
Q

Define adjuvant.

A

Substance added to vaccine antigens to enhance and modulate their immunogenicity.

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2
Q

Describe six (6) effects of adjuvants.

A
  1. Provide strong priming in naive individuals.
  2. Reduce the number of doses required to achieve protection.
  3. Increase the duration of the immune response.
  4. Enhance specific arms of the immune response.
  5. Increase the breadth of the immune response and enable cross-protection.
  6. Enhance the immune response in poorly responsive population.
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3
Q

What was the first new adjuvant based on Toll-like receptor activity?

A

Monophosphoryl lipid A.

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4
Q

In what vaccine was MPL-A first used?

A

Cervarix.

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5
Q

What is the principal mechanism by which the immune system is activated when encountering pathogens?

A

Recognition of pathogen-associated molecular patterns.

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6
Q

Name three (3) types of receptors linked to pathogen recognition.

A
  1. Toll-like receptors (TLRs).
  2. Retinoic-acid-inducible gene-based-I-like receptors (RLRs).
  3. Cytosolic nucleotide oligomerization domain (NOD)-like receptors (NLRs).
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7
Q

Name four (4) bacterial components that activate TLRs.

A
  1. Lipopeptides.
  2. Lipoteichoic acid.
  3. Flagellin.
  4. Lipopolysaccharides.
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8
Q

Name three (3) viral components that can activate TLRs.

A
  1. Double-stranded RNA.
  2. Single-stranded RNA.
  3. Viral DNA.
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9
Q

Name the four (4) main classes of adjuvants.

A
  1. Aluminum salts.
  2. Water-in-oil emulsions.
  3. Oil-in-water emulsions.
  4. TLR agonists.
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10
Q

Name three (3) aluminum salt adjuvants.

A
  1. Crystalline aluminum oxyhydroxide.
  2. Aluminum hydroxyphosphate sulfate.
  3. Aluminum potassium sulfate (alum).
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11
Q

What happens if a vaccine containing aluminum-based adjuvants is frozen?

A

Formation of caogulates which cannot be redispersed by shaking, rendering the vaccine unusable.

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12
Q

Name three (3) mechanisms responsible for the adsorption of antigens on the surface of the adjuvant.

A
  1. Electrostatic attraction.
  2. Hydrophobic forces.
  3. Ligand exchange.
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13
Q

Name three (3) potential mechanisms of action for aluminum-based adjuvants.

A
  1. Depot mechanism, i.e. salts remain at the injection site.
  2. Phagocytosis of adjuvant-antigen compounds by antigen-presenting cells.
  3. Direct stimulation of innate immune system pathways.
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14
Q

What lesion was potentially associated with aluminum salt adjuvants?

A

Macrophagic myofasciitis.

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15
Q

Name two (2) water-in-oil adjuvants.

A
  1. Fr
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16
Q

Why are water-in-oil adjuvants not recommended for use today?

A

Risk of cysts and/or abcesses at the injection site.

17
Q

What is the main oil-in-water adjuvant?

A

Squalene.

18
Q

What is the only vaccine currently in use that contain an oil-in-water adjuvant formulation?

A

FLUAD, an influenza vaccine (mainly for adults, pediatric version approved for use in Canada).

19
Q

What are the three (3) oil-in-water adjuvants currently approved for pandemic influenza vaccines?

A
  1. MF59.
  2. AS03.
  3. AF03.
20
Q

What are the two (2) main benefita of oil-in-water adjuvants for pandemic influenza vaccination?

A
  1. Highly effective priming, allowing for reduction of number of doses in the context of scarcity of supply.
  2. Enhanced diversity and affinity of antibodies.
21
Q

Briefly describe the components of the AS04 adjuvant.

A

MPL + aluminum salt.

22
Q

What are the two (2) main pathways activated by TLR4 agonists?

A
  1. Myeloid differentiation 88 (MyD88) pathway (proinflammatory response).
  2. TIR domain-containing adaptor-inducing IFN-ß (TRIF) pathway (type I interferon response).
23
Q

What is the main TLR9 agonist used as an adjuvant?

A

Cytosine phosphate guanine (CpG) motifs, found naturally in bacterial DNA.

24
Q

Describe briefly the composition of the AS01 adjuvant.

A

QS21 derived from Quil-A saponins + liposomes containing cholesterol + MPL

25
Q

What vaccine currently uses AS01 as an adjuvant?

A

Shingrix.

26
Q

Name four (4) experimental types of adjuvants.

A
  1. Saponins.
  2. Virosomes.
  3. Polyelectrolytes and polycations.
  4. Mucosal adjuvants.
27
Q

Name two (2) experimental mucosal adjuvants.

A
  1. V. cholerae holotoxin
  2. E. coli heat-labile enterotoxin