T1 L7 Vaccines and vaccine development

Question 1

What is immunisation?

Answer 1

An artificial process by which an individual is rendered immune

Question 2

What is passive immunisation?

Answer 2

Immunity conferred without active host response on behalf of recipient.

Question 3

What is active immunisation?

Answer 3

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

Question 4

Describe the historical background of variolation

Answer 4

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

Question 5

Describe the Jenner history of immunisation

Answer 5

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

Question 6

What are the preparations of passive vaccines?

Answer 6

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

Question 7

Give some examples of passive vaccines

Answer 7

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

Question 8

What is herd immunity?

Answer 8

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

Question 9

What type of response do most antibodies generate?

Answer 9

Long-lasting, high affinity IgG response

Question 10

What is contained within vaccine?

Answer 10

Antigen
Adjuvants
Excipients

Question 11

What is the function of antigens in the vaccine?

Answer 11

Stimulates antigen-specific B cell response

Question 12

What is the function of the adjuvants in the vaccine?

Answer 12

Immune potentiators to increase immunogenicity of the vaccine

Question 13

What is the function of the excipients in the vaccine?

Answer 13

Various diluents and additives required for vaccine integrity

Question 14

What are the subunits of active vaccines?

Answer 14

Toxoids
Capsular polysaccharide
Conjugated polysaccharide
Recombinant subunit

Question 15

Give examples of live-attenuated vaccines

Answer 15

Measles
Mumps
Rubella
Polio
BCG
Cholera
Zoster
VZV
Live influenza

Question 16

What are the benefits of live-attenuated vaccines?

Answer 16

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

Question 17

What are the cons of live-attenuated vaccines?

Answer 17

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

Question 18

Describe poliomyelitis

Answer 18

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

Question 19

Describe the Sabin oral polio vaccine (OPV)

Answer 19

Live-attenuated

Viable virus recovered from stool after immunisation

Question 20

Describe the Salk injected polio vaccine (IPV)

Answer 20

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

Question 21

Describe the primary infection of TB

Answer 21

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

Question 22

Describe the vaccine for TB

Answer 22

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

Question 23

How is BCG vaccine produced?

Answer 23

Repeat passage of non-tuberculosis mycobacterium

Question 24

What is a killed (inactivated) vaccine?

Answer 24

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

Question 25

Describe the response to a killed vaccine

Answer 25

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

Question 26

What are some examples of killed (inactivated) vaccines?

Answer 26

Hepatitis A | Influenza

Question 27

What are the benefits of killed (inactivated) vaccine?

Answer 27

No potential for reversion Safe for immunocompromised Stable in storage

Question 28

What are the cons of killed (inactivated vaccines)?

Answer 28

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

Question 29

Describe the structure of the influenza virus

Answer 29

``` 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) ```

Question 30

What are the difficulties of the influenza vaccine?

Answer 30

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

Question 31

What are subunit vaccines?

Answer 31

They only use the critical part of the organism

Question 32

What are the components of subunit vaccines?

Answer 32

Purified from organism | Generate by recombinant techniques

Question 33

What are benefits of subunit vaccines?

Answer 33

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

Question 34

What are the cons of subunit vaccines?

Answer 34

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

Question 35

Give examples of toxoids

Answer 35

Corynebacterium diphtheria Clostridium tetani Bordatella pertussis

Question 36

Describe the tetanus vaccine

Answer 36

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

Question 37

Why are streptococcus pneumonia and neisseria meningitidis resistant to phagocytosis?

Answer 37

Thick polysaccharide coat

Question 38

Why is a polysaccharide capsule suboptimal?

Answer 38

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

Question 39

What are the steps of vaccine conjugation?

Answer 39

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

Question 40

Why is vaccine development for HPV difficult?

Answer 40

HPV is difficult to culture

Question 41

What is the function of adjuvants?

Answer 41

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

Question 42

What are some examples of adjuvants?

Answer 42

Alum | Lipopolysaccharide

Question 43

Describe DNA vaccines

Answer 43

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

Question 44

Describe viral vectors

Answer 44

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