Darragh Murnane
Email:d.murnane@herts.ac.uk
Learning Objectives
To gain an understanding of immunization
To gain an understanding of vaccination strategies To gain an understanding of vaccine formulations
References
Antibodies, vaccines and adjuvants (Chp. 13) in Pharmaceutical Biotechnology, G Walsh.
Excipients used in vaccines (Chp. 18) in Excipient Development for Pharmaceutical, Biotechnology and Drug Delivery Systems, A Katdare & MV Chaubel (Eds)
Some definitions
Vaccine: an agent to promote active
immunization of an individual.
Prophylactic Traditionally an immunological agent to prevent infectious disease
Active immunity
Adaptive immunity:
Immune-mediating cells:
Macrophage, dendritic, neutrophils
Antigen presenting
T-cells
T-helper 1: cell-mediated immunity T-helper 2: involved in humoral response Natural killer cells (NK) kills own organism cells
B-cells
Humoral immunity (antibody production) Form memory cells
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Cell-mediated immunity
Antigen present within cell
Antigen presented on surface on MHC1 differentiate into killer or memory cells
Cell communication through helping molecules called interleukins. Using surface receptors to produce the required response.
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Killer T-cells kill cells expressing antigen on surface (apoptosis) Memory T-cells activated
Humoral immunity
Antigens presented on MHC2 in lymphatic system. Only specific cells do this (e.g. macrophages) Specific Th2 cell binds to antigen-presenting cell. Stimulates proliferation of Th2 cells by interleukins Th2 cells stimulate plasma and memory B-cells Plasma B cells produce antibodies, memory cells allow faster activation on re-exposure
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Vaccination
Vaccines are preparations containing antigens capable of inducing a specific and active immunity in man against an infecting agent or the toxin or antigen elaborated by it British Pharmacopoeia 2010
Vaccines may consist of dead, live (attenuated) organisms or Organism-derived antigens in native or detoxified state
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Routes of administration
Oral polio vaccine mucosal immunity Inhalation mucosal immunity (Flumist)
Stronger protective response than injection (Vaccine 26:383-98)
Inactivation
Chemical, heat treatment
Attenuation
chemical, heat treatment growth under adverse conditions or unnatural host
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Antigen preparation
Isolate toxin from growth, inactivate toxoid Traditional
Typically surface-derived polysaccharide antigens Conjugation to protein antigen
Future techniques??
Peptide synthesis, live non-pathogenic viruses
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Vaccine presentations
Live attenuated:
Typically lyophilized for stability Reconstituted in a buffer system
Inactivated/subunit vaccines
Typically suspensions in buffer Cholera suspension mixed with effervescent granules Typically require preservative May contain residues of growth media
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Adjuvant functions
Geographical immune reactivity Depot effect Stimulatory signals Induction of stimulatory signals
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Aluminium salts
Aluminium hydroxide/phosphate Biased to Th2 pathway May activate complement, depot effect. Increased IgE production allergenic
Emulsion Saponins
Non-ionic surfactants
Derivatives of lipopholysaccharides
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Formulation components
Preservatives
Phenol 2-Phenoxyethanol Thiomersal?
Salts
Na chloride, Na phosphate, succinate, Na borate Isotonicity, pH buffering.
Stabilizers
Sugars, amino acids, proteins Buffers, adsorption inhibition
Residues
Antibiotics, inactivating agents, cellular components
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Formulation performance
Temperature of storage 2 8 C The cold-chain difficulties Sterility and safe injection practices?
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ISCOMS
Immunostimulating complexes
protein antigen, cholesterol, phospholipid, Quil A (saponin adjuvant) Form cage-like nanopartilces (40 nm) that trap hydrophobic antigens in the core
ISCOMATRIX
Contains the same material (minus antigen)
Clinical experience for HPV, HIV, but concerns over toxicity of Quil A
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DNA Vaccines
DNA injected i.m. immune trigger
Broad immune response (1990s) Poor immunogenicity (e.g. HIV)
Types of product
Examples of HIV are PennvaxB delivered with IL12 (molecular adjuvant) and electroporesis.
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