T1 L7 Vaccines and vaccine development Flashcards
What is immunisation?
An artificial process by which an individual is rendered immune
What is passive immunisation?
Immunity conferred without active host response on behalf of recipient.
What is active immunisation?
Immunity conferred in recipient following generation of adaptive-immune response
Stimulates adaptive immune response without causing clinically-apparent infection
Describe the historical background of variolation
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
Describe the Jenner history of immunisation
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
What are the preparations of passive vaccines?
Antibodies taken from hyper-immune donors which can be human or animal
Give some examples of passive vaccines
Immunoglobulin replacement in antibody deficiency
VZV prophylaxis e.g. exposure during pregnancy
Anti-toxin therapies e.g. snake anti-serum
What is herd immunity?
Vaccination of sufficient numbers impacts transmission dynamic so unimmunised individuals are at low risk
What type of response do most antibodies generate?
Long-lasting, high affinity IgG response
What is contained within vaccine?
Antigen
Adjuvants
Excipients
What is the function of antigens in the vaccine?
Stimulates antigen-specific B cell response
What is the function of the adjuvants in the vaccine?
Immune potentiators to increase immunogenicity of the vaccine
What is the function of the excipients in the vaccine?
Various diluents and additives required for vaccine integrity
What are the subunits of active vaccines?
Toxoids
Capsular polysaccharide
Conjugated polysaccharide
Recombinant subunit
Give examples of live-attenuated vaccines
Measles Mumps Rubella Polio BCG Cholera Zoster VZV Live influenza
What are the benefits of live-attenuated vaccines?
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
What are the cons of live-attenuated vaccines?
Storage problems, short shelf life
May revert to wild type –> vaccine associated poliomyelitis
Immunocompromised recipients may develop clinical disease
Describe poliomyelitis
Enterovirus establishes infection in oropharynx and GI tract
Spreads to peyers patches then disseminated via lymphatics
Haematogenous spread
1% patients develop neurological phase
Describe the Sabin oral polio vaccine (OPV)
Live-attenuated
Viable virus recovered from stool after immunisation
Describe the Salk injected polio vaccine (IPV)
Inactivated
Effective but herd immunity inferior
UK switched to IPV in 2004
Describe the primary infection of TB
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
Describe the vaccine for TB
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
How is BCG vaccine produced?
Repeat passage of non-tuberculosis mycobacterium
What is a killed (inactivated) vaccine?
Entire organism is used after physical or chemical methods are used to destroy viability such as formaldehyde
Describe the response to a killed vaccine
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
What are some examples of killed (inactivated) vaccines?
Hepatitis A
Influenza
What are the benefits of killed (inactivated) vaccine?
No potential for reversion
Safe for immunocompromised
Stable in storage
What are the cons of killed (inactivated vaccines)?
Mainly CD4 / antibody response
Response is less durable than live vaccines - boosters are normally required
Higher uptake needed to achieve herd immunity
Describe the structure of the influenza virus
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)
What are the difficulties of the influenza vaccine?
Target antigens are prone to mutation (antigenic drift) causing seasonal variation so vaccine is based on predictions
What are subunit vaccines?
They only use the critical part of the organism
What are the components of subunit vaccines?
Purified from organism
Generate by recombinant techniques
What are benefits of subunit vaccines?
Extremely safe
Works well where primary infection may be prevented by an antibody response
Works when virus can’t easily be cultured
What are the cons of subunit vaccines?
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
Give examples of toxoids
Corynebacterium diphtheria
Clostridium tetani
Bordatella pertussis
Describe the tetanus vaccine
Pre-formed high-affinity IgG antibodies can neutralise toxin molecules in circulation. Immune complexes are then removed via spleen
Why are streptococcus pneumonia and neisseria meningitidis resistant to phagocytosis?
Thick polysaccharide coat
Why is a polysaccharide capsule suboptimal?
Polysaccharides are weakly immunogenic
No protein / peptide means no T cell response
Stimulate small population of T-independent B-cells
What are the steps of vaccine conjugation?
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
Why is vaccine development for HPV difficult?
HPV is difficult to culture
What is the function of adjuvants?
Boost immune response to antigen
Bind to pattern-recognition receptors to enhance co-stimulation and cytokine secretion to ensure robust T/B cell response
What are some examples of adjuvants?
Alum
Lipopolysaccharide
Describe DNA vaccines
Plasmid DNA that encodes vaccine antigen of interest applied –> taken up by cells –> transcribed and translated
Elicits host immune response
Describe viral vectors
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
