vaccination student notes
TRANSCRIPT
-
8/14/2019 Vaccination Student Notes
1/24
Travel Medicine
Darragh MurnaneEmail:[email protected]
Vaccination strategies & formulation
-
8/14/2019 Vaccination Student Notes
2/24
2
To gain an understanding ofimmunization
To gain an understanding of vaccination
strategies
To gain an understanding of vaccine
formulations
Learning Objectives
-
8/14/2019 Vaccination Student Notes
3/24
3
References
Antibodies, vaccines and adjuvants (Chp. 13) inPharmaceutical Biotechnology, G Walsh.
Excipients used in vaccines (Chp. 18) in
Excipient Development for Pharmaceutical,
Biotechnology and Drug Delivery Systems, A
Katdare & MV Chaubel (Eds)
The Green Book:http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/Publ
icationsPolicyAndGuidance/DH_079917
-
8/14/2019 Vaccination Student Notes
4/24
4
Some definitions
Vaccine: an agent to promote activeimmunization of an individual.
Prophylactic
Traditionally an immunological agent to prevent
infectious disease
Immunization: the production of immunity by
artificial means
Immunity: resistance of an organism to a
particular infection or toxin by the action of
antibodies or sensitized white blood cells.
-
8/14/2019 Vaccination Student Notes
5/24
Active immunityAdaptive 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
5
-
8/14/2019 Vaccination Student Notes
6/24
Cell-mediated immunity
Antigen present within
cell
Antigen presented on
surface on MHC1differentiate into killer or
memory cells
Killer T-cells kill cellsexpressing antigen on
surface (apoptosis)
Memory T-cells activated6
Cell communication throughhelping molecules calledinterleukins. Using surfacereceptors to produce therequired response.
-
8/14/2019 Vaccination Student Notes
7/24
Humoral immunityAntigens presented on
MHC2 in lymphatic system.
Only specific cells do this
(e.g. macrophages)
Specific Th2 cell binds toantigen-presenting cell.
Stimulates proliferation of
Th2 cells by interleukins
Th2 cells stimulate plasma
and memory B-cells
7
Plasma B cells produce antibodies, memory cells allow faster
activation on re-exposure
-
8/14/2019 Vaccination Student Notes
8/24
Humoral immunity - antibodies
Immunoglobulin proteins which bindspecifically to an antigen
Fc region binds to host cell surface
receptors (e.g. macrophages)Neutralize and immobilize pathogens
IgG/IgMmain circulating Abs
IgAfound on mucosal surfaces
IgEallergic reactions/exoparisites
8
Antibodies from initial infection take up to 2 weeks to peak
Second infectionpeak faster (2 days) and levels remain higher
-
8/14/2019 Vaccination Student Notes
9/24
Infectious diseasetravel
Immunity built over life-long exposure
Travel exposes individuals to unknown organisms
Uncharacteristic behaviour (e.g. Hep B)
Vaccination prevents against infection with
serious diseases
See current UK vaccination: The Green BookFor information on travel vaccination:http://www.nhs.uk/Conditions/Travel-immunisation/Pages/Introduction.aspx
9
-
8/14/2019 Vaccination Student Notes
10/24
Vaccination
Vaccines are preparations containing antigenscapable of inducing a specific and active
immunity in man against an infecting agent or
the toxin or antigen elaborated by it
British Pharmacopoeia 2010
10
Vaccines may consist of dead, live (attenuated) organisms
or
Organism-derived antigens in native or detoxified state
-
8/14/2019 Vaccination Student Notes
11/24
Routes of administration
Oral polio vaccinemucosal immunity
Inhalationmucosal immunity (Flumist)
Stronger protective response than injection
(Vaccine 26:383-98)
Intramuscularinteraction with lymph and
circulatory systems
Subcutaneous/intradermal routesgood
interaction with dendritic cells
11
-
8/14/2019 Vaccination Student Notes
12/24
Types of vaccine preparations
Inactivated (killed) organisms
Attenuated (avirulent) live organisms
Secreted products (antigens). Tetnus anddiptheria
Recombinant components (antigens)
Components of cell walls (antigens)
influenza vaccine
12
-
8/14/2019 Vaccination Student Notes
13/24
Antigen production techniques
Growth Bacteria in medium, viruses in fertilized eggs
or cell culture
Inactivation Chemical, heat treatment
Attenuation
chemical, heat treatment
growth under adverse conditions or unnatural
host
13
-
8/14/2019 Vaccination Student Notes
14/24
Antigen preparationIsolate toxin from growth, inactivatetoxoid
Traditional
Typically surface-derived polysaccharide
antigens
Conjugation to protein antigen
Recombinant techniques - subunit
Produce polypeptide in non-pathogenic host
Unlimited supply of defined product, no viralcontamination
Future techniques??
Peptide synthesis, live non-pathogenic viruses14
-
8/14/2019 Vaccination Student Notes
15/24
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
15
-
8/14/2019 Vaccination Student Notes
16/24
The role of adjuvant
structurally heterogeneous compounds used toevoke/increase an immune response
Required for non-live vaccine systems
Must be co-administered, mechanism poorly
understood
Stablelong shelf-life
Biodegradable Cheap
Immunologically inert
Promote immune response
16
-
8/14/2019 Vaccination Student Notes
17/24
Adjuvant functions
Geographical immune reactivity
Depot effect
Stimulatory signals
Induction of stimulatory signals
17
-
8/14/2019 Vaccination Student Notes
18/24
Aluminium salts
Aluminium hydroxide/phosphate
Biased to Th2 pathway
May activate complement, depot effect.
Increased IgE productionallergenic
Emulsion
Saponins Non-ionic surfactants
Derivatives of lipopholysaccharides
18
-
8/14/2019 Vaccination Student Notes
19/24
Formulation componentsPreservatives
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
19
-
8/14/2019 Vaccination Student Notes
20/24
Formulation performance
Temperature of storage 2
8 C
The cold-chain difficulties
Sterility and safe injection practices?
Requirement for booster dosescompliance?
Poor immunological responsenovel systems
ISCOMSimproved Th1 response
Increase potency
Microparticle pulsatile releasee.g. PLGA
Particulate may stabilize vaccine but sterile reconstitution?
Particulates may promote Th1 response
Mucosal vaccination approaches?20
-
8/14/2019 Vaccination Student Notes
21/24
Some recent advances
21
Virus-like particles
First generation HepB (e.g. Engerix B)
Small viral envelope protein expressed in yeast
form 22 nm particles.
Gardasil (human papilloma virus)
Self-assembled L1 capsid proteins
Aluminium salt adjuvant - 90 % reduction in HPV
infection
-
8/14/2019 Vaccination Student Notes
22/24
ISCOMSImmunostimulating 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 A22
-
8/14/2019 Vaccination Student Notes
23/24
DNA VaccinesDNA injected i.m.immune trigger
Broad immune response (1990s)
Poor immunogenicity (e.g. HIV)
2nd
generationuse of plasmid vectors (e.g. Liposomes), stimulate CD8+cytotoxic
cells
PMED (Pfizer)plasmid/vector + gold
nanoparticles with a high pressure delivery
Antigen expressed by bodys own cells
Potentially safe because no infectious agents
23
-
8/14/2019 Vaccination Student Notes
24/24
Types of product
24
Examples of HIV are PennvaxB delivered with IL12 (molecular
adjuvant) and electroporesis.