Vaccine Development Flashcards
What types of diseases can be controlled by vaccines?
Poorly infectious
Antigens relatively invariant
What types of diseases are difficult to control by vaccines?
High infectious
Antigenic variation
Animal or environmental reservoirs of infection
What is the aim of vaccination?
To induce the specific immunity to:
Prevent microbial invasion
Eliminate microbes
Neutralize microbial toxins
What are the properties of central memory T cells?
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
What are the properties of effector memory T cells?
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
Define active immunization
Patient mounts a protective immune response
Define passive immunisation
Acquires immunity through transfer of antibodies
What are the features of attenuated (live) vaccines?
Use pathogens Mild infections Active microbes Strong immune response Effective with one does Contact immunity Hazardous
What are the features of inactivated vaccines?
Whole agent vaccines Subunit vaccines Safer than live vaccines Antigenically weak Often contain adjuvants
What can be used in inactivated vaccines?
Viruses
Bacteria
Protein based
Polysaccharide-based
Name some adjuvants and their uses
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
What are the features of a toxoid vaccine?
Modified toxins
Useful for some bacterial diseases
Antibody-mediated immunity
Require multiple doses
What are the problems associated with immunisation?
Mild toxicity Pain or general malaise Anaphylactic shock Virulence Autism, diabetes and asthma
What are the limitations to passive immunisation?
Antibodies against many antigens Serum sickness May be contaminated with virus Antibodies degraded quickly May be overcome through development of hybridomas
How is a hybridoma made?
- A mouse is injected with antigen
- Plasma cells, which secrete antibodies, are removed from the spleen
- Plasma cells and myeloma cells are fused, they are long lived and produce antibodies
- Hybridomas are placed individually in small wells and tested for reactivity against the antigen
- The hybridoma that reacts with the antigen is cloned
What are the properties of an ideal vaccine?
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
What are the obstacles to a Malaria vaccine?
Plasmodium parasites have 5,000 genes Complex life cycle Different developmental stages Humans can be repeatedly re-infected Parasite evasion strategies
What are the different types of vaccines that target different Malaria life cycle stages?
Pre-erythrocytic vaccines (Pre-RBC/Sporozoite)
Blood stage vaccines (RBC)
Transmission-blocking vaccines (Mosquito stages)
Describe the features of RTS,S Malaria
Partially protects children (18 months)
Fusion protein of circumsporozoite protein, hep B surface antigen, adjuvant AS02
What are the features of Sanaria?
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
What is the basis of therapeutic cancer vaccines?
Target recognised by T and B cells
Tumour antigens have poor immunogenicity
Tolerated in the host
How do you identify tumour-associated antigens?
Peptides eluded from MHC complexes on tumour cell membranes
Test candidate tumour antigens by reverse immunology
What are the types of therapeutic cancer vaccines?
Tumor cell vaccines Antigen vaccines use tumor-specific antigens Dendritic cell vaccines Anti-idiotypic vaccines DNA vaccines Vector-based vaccines
What are the features of Sipuleucel-T (Provenge)?
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
What is the possible mechanism of action of provenge?
- Recombinant PAP antigen combines with resting APC
- APC takes up antigen
- Antigen is processed and presented on surface of APC
- Fully activated, the APC is now sipuleucel-T
- infused into patient
- Sipuleucel-T activated T-cells in the body
- T-cells proliferate and attack cancer cells
