Lecture 34 - Vaccines Flashcards

1
Q

Difference between an antigen and an immunogen

A

An antigen is defined as ANtibody GENerating

An immunogen elicits an immune response (is more general)

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2
Q

Passive vaccination sources
1)
2)
3)

A

1) Human Ig preparations from pooled human sera
2) Specific human Ig from pooled human serum
3) Animal-derived serum antibodies or antitoxins

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3
Q

When are passive vaccines useful?

A

When there is no time for the body to mount an immune response (EG: snake bite)

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4
Q

Broad definition of a vaccine

A

Elicit an immune response to protect form infectious disease

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5
Q
Experimental vaccine approaches
1)
2)
3)
4)
A

1) Cure existing disease (therapeutic)
2) Block physiology (hormones, fertility)
3) Prevent, cure cancers
4) Prevent, cure autoimmune disorders (EG: allergies)

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6
Q

Requirements for a vaccine
1)
2)
3)

A

1) Efficacious
2) Safe
3) Affordable

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7
Q

Do vaccinations prevent infections?

A

No. They shorten the exponential phase of replication, resulting in a subclinical infection

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8
Q
Things to consider when designing a vaccine
1)
2)
3)
4)
5)
A

1) Where does the body first encounter the pathogen
2) Which parts of the body does the pathogen encounter
3) Virulence factors produced by pathogen
4) Extent of antigenic variation of virulence factor
5) How is antigen to be presented to the immune system

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9
Q

Vaccine approach for toxin-secreting bacteria

A

Give multiple vaccines, to ensure that antibody titre is high enough to neutralise toxin

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10
Q

Vaccine design consideration for antigenic diversity of virulence determinant

A

Include all virulence determinants, or just the dominant ones?

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11
Q
How to enhance vaccine immunogenicity
1)
2)
3)
4)
A

1) Elicit the correct type of immune response (Th1 or Th2 mediated)
2) Adjuvants
3) Target innate immunity (DCs) to program adaptive immunity
4) Target the correct branch of the immune system(mucosal immunity versus tissue immunity)

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12
Q
Bordatella pertussis
1)
2)
3)
4)
A

1) Gram -, small coccobacillus
2) Spread by aerosols
3) PTX, AC toxins
4) P69, fim, FHA adhesins

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13
Q

How can vaccine efficacy be tested?

A

Kendrick test

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14
Q

Kendrick test
1)
2)
3)

A

1) Administer vaccine to animal intraperitoneally
2) Challenge animal with intracranial antigen
3) If vaccine works, mice don’t die

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15
Q

Old pertussis vaccine

A

Whole cell killed vaccine

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16
Q

Problems with old pertussis vaccine

A

Very immunogenic, as contains LPS

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17
Q
Tetanus vaccine
1)
2)
3)
4)
5)
A

1) Old vaccine
2) Over 95% effective
3) Inactivated tetanospasmin toxoid
4) Induces toxin-neutralising antibodies
5) Inhibits disease, not infection

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18
Q

Proportion of neonatal deaths due to tetanus in 1993 compared to now

A

14% versus 5%

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19
Q

Name for an inactivated toxin

20
Q

Can clostridium tetani be eradicated?

A

No.

Ubiquitous in soil

21
Q

Most common cause of meningitis in children

A

Haemophilus influenzae

22
Q

When does immunity to H influenzae develop?

A

10-16 years of age

23
Q

Consequence of H influenzae capsule inhibiting C3b binding
1)
2)

A

1) Not opsonised, evades phagocytosis

2) Growth is uncontrolled, causes septic shock

24
Q

T-dependent B cell antibody pathway
1)
2)
3)

A

1) T cell binds cognate antigen presented on MHCII by B cell
2) CD4+ releases IL-2, IL-4, IL-5
3) B cell is activated, proliferates, matures

25
``` T-cell-independent B cell antibody pathway 1) 2) 3) 4) ```
1) Repetitive molecule (EG: capsule polysaccharide) crosslinks BCR 2) B cell PAMP or DAMP is activated 3) B cell is activated, proliferates, matures 4) IgM is produced, no memory
26
What type of vaccine is the H influenzae vaccine?
Conjugated polysaccharide
27
Polysaccharide component of H influenzae vaccine
Linear polymer of ribosyl | Ribitol phosphate is part of the H influenzae capsule
28
``` How can polysaccharide vaccines induce memory? 1) 2) 3) 4) ```
1) Conjugation 2) Carbohydrate antigen is conjugated to a protein antigen (EG: tetanus toxoid, cholera toxoid) 3) Cognate B cell takes up carbohydrate/protein antigen, presents protein antigen on MHCII 4) CD4+ recognises MHCII/antigen, secretes interleukins (EG: IL-4 from Th2) for B cell activation, isotype switching, memory
29
What does alum do?
Forms complexes with antigen, keeps antigen presentable to the immune system for longer
30
Number of serotypes of strep pneumoniae
Over 90
31
Is Strep pneumoniae a normal part of human flora?
Yes. | Asymptomatically colonises URT
32
Type of bacteria that Strep pneumoniae is
Gram + diplococcus
33
Pneumolysin effect
Inhibits beating of cilia in airways
34
Two vaccines for Strep pneumoniae
1) Polysaccharide vaccine (of capsule, 23 different polysacchrides) 2) Protein conjugate vaccine (13 capsular polysaccharides)
35
What is serotype replacement disease?
When certain Strep pneumoniae serotypes are vaccinated against, other, less common types begin causing disease
36
Results of vaccination with 7-valent pneumococcal conjugate vaccine
Invasive pneumococcal disease with 7-valent S pneumoniae dropped between 2002-2007 Non-7-valent Strep pneumoniae rates of invasive pneumococcal disease increased between 2002-2007
37
Australian population at risk of invasive pneumococal disease
Aboriginal (particularly children)
38
Vaccines which provide no protective response
Salmonella, cholera, tuberculosis
39
Vaccine that failed because of side-effects
Rotavirus vaccine caused intestinal blockage in children
40
Vaccines that improved disease in animal models, but worsened disease in humans
RSV, Chlamydia trachomatis
41
Way to target mucosal immunity
Non-injection adminstration
42
How can you reduce the risk of live-attenuated vaccines reverting to virulence?
Encode more than one mutation
43
How do DNA vaccines work?
Inject DNA, which encodes antigens for the immune system to react to
44
What does alum help induce?
Antibody responses
45
Problem with alum as an adjuvant
Preferentially induces an antibody repsonse
46
Reverse vaccinology 1) 2) 3)
1) Sequence genome of bacteria 2) Look for expressed proteins 3) Observe effect of proteins in animal models