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

A

Toxoid

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
Q
T-cell-independent B cell antibody pathway
1)
2)
3)
4)
A

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
Q

What type of vaccine is the H influenzae vaccine?

A

Conjugated polysaccharide

27
Q

Polysaccharide component of H influenzae vaccine

A

Linear polymer of ribosyl

Ribitol phosphate is part of the H influenzae capsule

28
Q
How can polysaccharide vaccines induce memory?
1)
2)
3)
4)
A

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
Q

What does alum do?

A

Forms complexes with antigen, keeps antigen presentable to the immune system for longer

30
Q

Number of serotypes of strep pneumoniae

A

Over 90

31
Q

Is Strep pneumoniae a normal part of human flora?

A

Yes.

Asymptomatically colonises URT

32
Q

Type of bacteria that Strep pneumoniae is

A

Gram + diplococcus

33
Q

Pneumolysin effect

A

Inhibits beating of cilia in airways

34
Q

Two vaccines for Strep pneumoniae

A

1) Polysaccharide vaccine (of capsule, 23 different polysacchrides)
2) Protein conjugate vaccine (13 capsular polysaccharides)

35
Q

What is serotype replacement disease?

A

When certain Strep pneumoniae serotypes are vaccinated against, other, less common types begin causing disease

36
Q

Results of vaccination with 7-valent pneumococcal conjugate vaccine

A

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
Q

Australian population at risk of invasive pneumococal disease

A

Aboriginal (particularly children)

38
Q

Vaccines which provide no protective response

A

Salmonella, cholera, tuberculosis

39
Q

Vaccine that failed because of side-effects

A

Rotavirus vaccine caused intestinal blockage in children

40
Q

Vaccines that improved disease in animal models, but worsened disease in humans

A

RSV, Chlamydia trachomatis

41
Q

Way to target mucosal immunity

A

Non-injection adminstration

42
Q

How can you reduce the risk of live-attenuated vaccines reverting to virulence?

A

Encode more than one mutation

43
Q

How do DNA vaccines work?

A

Inject DNA, which encodes antigens for the immune system to react to

44
Q

What does alum help induce?

A

Antibody responses

45
Q

Problem with alum as an adjuvant

A

Preferentially induces an antibody repsonse

46
Q

Reverse vaccinology
1)
2)
3)

A

1) Sequence genome of bacteria
2) Look for expressed proteins
3) Observe effect of proteins in animal models