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Module 204 MSK & Immune system > T1 L7 Vaccines and vaccine development > Flashcards

T1 L7 Vaccines and vaccine development Flashcards

1
Q

What is immunisation?

A

An artificial process by which an individual is rendered immune

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2
Q

What is passive immunisation?

A

Immunity conferred without active host response on behalf of recipient.

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3
Q

What is active immunisation?

A

Immunity conferred in recipient following generation of adaptive-immune response
Stimulates adaptive immune response without causing clinically-apparent infection

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4
Q

Describe the historical background of variolation

A

Variola = smallpox virus
Fluid is harvested from pustules of recovering individuals and injected under skin of recipient.

Documented practice in Far Easter, Middle East and South Asia from 1000AD

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5
Q

Describe the Jenner history of immunisation

A

Used fluid from cowpox lesions to protect against smallpox infection in 1796
Subsequently experimented with several other children, including his own infant son
1st documented use of live-attenuated vaccine and birth of modern immunisation

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6
Q

What are the preparations of passive vaccines?

A

Antibodies taken from hyper-immune donors which can be human or animal

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7
Q

Give some examples of passive vaccines

A

Immunoglobulin replacement in antibody deficiency
VZV prophylaxis e.g. exposure during pregnancy
Anti-toxin therapies e.g. snake anti-serum

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8
Q

What is herd immunity?

A

Vaccination of sufficient numbers impacts transmission dynamic so unimmunised individuals are at low risk

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9
Q

What type of response do most antibodies generate?

A

Long-lasting, high affinity IgG response

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10
Q

What is contained within vaccine?

A

Antigen
Adjuvants
Excipients

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11
Q

What is the function of antigens in the vaccine?

A

Stimulates antigen-specific B cell response

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12
Q

What is the function of the adjuvants in the vaccine?

A

Immune potentiators to increase immunogenicity of the vaccine

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13
Q

What is the function of the excipients in the vaccine?

A

Various diluents and additives required for vaccine integrity

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14
Q

What are the subunits of active vaccines?

A

Toxoids
Capsular polysaccharide
Conjugated polysaccharide
Recombinant subunit

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15
Q

Give examples of live-attenuated vaccines

A 
Measles
Mumps
Rubella
Polio
BCG
Cholera
Zoster
VZV
Live influenza
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16
Q

What are the benefits of live-attenuated vaccines?

A

Replication within host produces highly effective and durable response
In viral vaccine, intracellular infection leads to good CD8 response
Repeated boosting isn’t required
Some diseases you can get secondary protection of unvaccinated individuals who are infected with live-attenuated vaccine strain

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17
Q

What are the cons of live-attenuated vaccines?

A

Storage problems, short shelf life
May revert to wild type –> vaccine associated poliomyelitis
Immunocompromised recipients may develop clinical disease

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18
Q

Describe poliomyelitis

A

Enterovirus establishes infection in oropharynx and GI tract
Spreads to peyers patches then disseminated via lymphatics
Haematogenous spread
1% patients develop neurological phase

19
Q

Describe the Sabin oral polio vaccine (OPV)

A

Live-attenuated

Viable virus recovered from stool after immunisation

20
Q

Describe the Salk injected polio vaccine (IPV)

A

Inactivated
Effective but herd immunity inferior
UK switched to IPV in 2004

21
Q

Describe the primary infection of TB

A

1) MTB establishes infection within phago-lysosomes of macrophages
2) Macrophages present TB antigen to MTB specific CD4 T-cells
3) Secrete IFN-gamma
4) Activates macrophages
5) Encase TB in granuloma

22
Q

Describe the vaccine for TB

A

BCG (bacili Calmette-Guerin) is only licensed product.
Aims to increase Th1 cell responses to M Boris which confers protection against MTB
Given by intradermal injection

23
Q

How is BCG vaccine produced?

A

Repeat passage of non-tuberculosis mycobacterium

24
Q

What is a killed (inactivated) vaccine?

A

Entire organism is used after physical or chemical methods are used to destroy viability such as formaldehyde

25
Q

Describe the response to a killed vaccine

A

Stimulates B cells to take up antigen and become antigen-presenting cells to stimulate antigen-specific CD4 T-cells
Elicit minimal CD8 response as vaccine can’t undergo intracellular replication
Response is less robust compared to live-attenuated

26
Q

What are some examples of killed (inactivated) vaccines?

A

Hepatitis A

Influenza

27
Q

What are the benefits of killed (inactivated) vaccine?

A

No potential for reversion
Safe for immunocompromised
Stable in storage

28
Q

What are the cons of killed (inactivated vaccines)?

A

Mainly CD4 / antibody response
Response is less durable than live vaccines - boosters are normally required
Higher uptake needed to achieve herd immunity

29
Q

Describe the structure of the influenza virus

A 
Internal antigens (matrix & RNP) are type-specific proteins used to determine whether a virus is A, B or C
External antigens (haemagglutinin and neuraminidase) are subtype and strain-specific antigens of influenza A virus (H1N1, H2N2, H3N2)
30
Q

What are the difficulties of the influenza vaccine?

A

Target antigens are prone to mutation (antigenic drift) causing seasonal variation so vaccine is based on predictions

31
Q

What are subunit vaccines?

A

They only use the critical part of the organism

32
Q

What are the components of subunit vaccines?

A

Purified from organism

Generate by recombinant techniques

33
Q

What are benefits of subunit vaccines?

A

Extremely safe
Works well where primary infection may be prevented by an antibody response
Works when virus can’t easily be cultured

34
Q

What are the cons of subunit vaccines?

A

Development requires detailed knowledge of virology, pathogenesis and immunology
Specialised and expensive production
Weaker immune response so boosting is often needed and response rate variess

35
Q

Give examples of toxoids

A

Corynebacterium diphtheria
Clostridium tetani
Bordatella pertussis

36
Q

Describe the tetanus vaccine

A

Pre-formed high-affinity IgG antibodies can neutralise toxin molecules in circulation. Immune complexes are then removed via spleen

37
Q

Why are streptococcus pneumonia and neisseria meningitidis resistant to phagocytosis?

A

Thick polysaccharide coat

38
Q

Why is a polysaccharide capsule suboptimal?

A

Polysaccharides are weakly immunogenic
No protein / peptide means no T cell response
Stimulate small population of T-independent B-cells

39
Q

What are the steps of vaccine conjugation?

A

1) Naive B-cell expressive surface IgM recognises polysaccharide antigen
2) Antigen is internalised with protein conjugate
3) Conjugate is processed in class II pathway
4) Naive B-cell presents peptides from conjugate to helper T cell with correct receptor
5) T-cell helps B-cell reform affinity maturation

40
Q

Why is vaccine development for HPV difficult?

A

HPV is difficult to culture

41
Q

What is the function of adjuvants?

A

Boost immune response to antigen
Bind to pattern-recognition receptors to enhance co-stimulation and cytokine secretion to ensure robust T/B cell response

42
Q

What are some examples of adjuvants?

A

Alum

Lipopolysaccharide

43
Q

Describe DNA vaccines

A

Plasmid DNA that encodes vaccine antigen of interest applied –> taken up by cells –> transcribed and translated
Elicits host immune response

44
Q

Describe viral vectors

A

Benign virus that can easily be grown in culture is engineered to carry genes encoding immunogenic antigens
Altered virus is used as live-attenuated vaccine

Module 204 MSK & Immune system (44 decks)

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