Vaccine Development

Question 1

What types of diseases can be controlled by vaccines?

Answer 1

Poorly infectious

Antigens relatively invariant

Question 2

What types of diseases are difficult to control by vaccines?

Answer 2

High infectious
Antigenic variation
Animal or environmental reservoirs of infection

Question 3

What is the aim of vaccination?

Answer 3

To induce the specific immunity to:
Prevent microbial invasion
Eliminate microbes
Neutralize microbial toxins

Question 4

What are the properties of central memory T cells?

Answer 4

Transient antigenic stimulation
Localised to the secondary lymphoid tissue
CCR7 positive
CD127 positive
CD28 positive
May be perforin positive/negative
Highly positive for proliferative capacity
Protect against viral acquisition positive/negative
Highly positive protection against viraemia

Question 5

What are the properties of effector memory T cells?

Answer 5

Persistent antigenic stimulation
Localised in mucosal tissue
CDR7 negative
CD127 negative
CD28 negative
Highly positive for perforin
Pos/neg for proliferative capacity
highly protective against viral acquisition
Negative protection against viraemia

Question 6

Define active immunization

Answer 6

Patient mounts a protective immune response

Question 7

Define passive immunisation

Answer 7

Acquires immunity through transfer of antibodies

Question 8

What are the features of attenuated (live) vaccines?

Answer 8

Use pathogens
Mild infections
Active microbes
Strong immune response
Effective with one does
Contact immunity
Hazardous

Question 9

What are the features of inactivated vaccines?

Answer 9

Whole agent vaccines
Subunit vaccines
Safer than live vaccines
Antigenically weak
Often contain adjuvants

Question 10

What can be used in inactivated vaccines?

Answer 10

Viruses
Bacteria
Protein based
Polysaccharide-based

Question 11

Name some adjuvants and their uses

Answer 11

Aluminium phosphates-slows processing and degredation of antigen
Saporin- stimulates T cell responses
Mineral oil- Slows processing and degradation of antigen
Freunds complete adjuvant- slows processing and degradation of antigen, stimulates T cell responses

Question 12

What are the features of a toxoid vaccine?

Answer 12

Modified toxins
Useful for some bacterial diseases
Antibody-mediated immunity
Require multiple doses

Question 13

What are the problems associated with immunisation?

Answer 13

Mild toxicity
Pain or general malaise
Anaphylactic shock
Virulence
Autism, diabetes and asthma

Question 14

What are the limitations to passive immunisation?

Answer 14

Antibodies against many antigens
Serum sickness
May be contaminated with virus
Antibodies degraded quickly
May be overcome through development of hybridomas

Question 15

How is a hybridoma made?

Answer 15

1. A mouse is injected with antigen
2. Plasma cells, which secrete antibodies, are removed from the spleen
3. Plasma cells and myeloma cells are fused, they are long lived and produce antibodies
4. Hybridomas are placed individually in small wells and tested for reactivity against the antigen
5. The hybridoma that reacts with the antigen is cloned

Question 16

What are the properties of an ideal vaccine?

Answer 16

Safe
Affordable
Heat stable
Effective in a single dose
Applicable to a number of diseases
Administered by a mucosal route
Suitable for admin early in life

Question 17

What are the obstacles to a Malaria vaccine?

Answer 17

Plasmodium parasites have 5,000 genes
Complex life cycle
Different developmental stages
Humans can be repeatedly re-infected
Parasite evasion strategies

Question 18

What are the different types of vaccines that target different Malaria life cycle stages?

Answer 18

Pre-erythrocytic vaccines (Pre-RBC/Sporozoite)
Blood stage vaccines (RBC)
Transmission-blocking vaccines (Mosquito stages)

Question 19

Describe the features of RTS,S Malaria

Answer 19

Partially protects children (18 months)

Fusion protein of circumsporozoite protein, hep B surface antigen, adjuvant AS02

Question 20

What are the features of Sanaria?

Answer 20

Raise mosquitoes in sterile environment
Sporozoites from mosquito salivary glands
Free of pathogens
Free of mosquito salivary gland material
Attenuated by irradiation
Potent
Injection to induce protection

Question 21

What is the basis of therapeutic cancer vaccines?

Answer 21

Target recognised by T and B cells
Tumour antigens have poor immunogenicity
Tolerated in the host

Question 22

How do you identify tumour-associated antigens?

Answer 22

Peptides eluded from MHC complexes on tumour cell membranes

Test candidate tumour antigens by reverse immunology

Question 23

What are the types of therapeutic cancer vaccines?

Answer 23

Tumor cell vaccines
Antigen vaccines use tumor-specific antigens
Dendritic cell vaccines
Anti-idiotypic vaccines 
DNA vaccines
Vector-based vaccines

Question 24

What are the features of Sipuleucel-T (Provenge)?

Answer 24

Tumor-associated antigen
Prostatic acid phosphatase (PAP)
Autologous active cellular vaccine
Recombinant fusion protein PA2024, PAP-linked to granulocyte macrophages
GM-CSF
Activates IS against prostate cancer
T-cell specific activity to P2024 and PAP
Antibodies

Question 25

What is the possible mechanism of action of provenge?

Answer 25

1. Recombinant PAP antigen combines with resting APC
2. APC takes up antigen
3. Antigen is processed and presented on surface of APC
4. Fully activated, the APC is now sipuleucel-T
5. infused into patient
6. Sipuleucel-T activated T-cells in the body
7. T-cells proliferate and attack cancer cells