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Vaccine Delivery Systems
Vaccine Delivery Systems
INTRODUCTION:
The word “vaccine” originates from the Latin Variolae vaccinea (cowpox), which Edward
Jenner demonstrated in 1798 could prevent smallpox in humans. Today the term ‘vaccine’
applies to all biological preparations, produced from living organisms, that enhance immunity
against disease and either prevent (prophylactic vaccines) or, in some cases, treat disease
(therapeutic vaccines).
Vaccines are administered in liquid form, either by injection, by oral, or by intranasal routes.
Ex. Polio , Hepatitis –A……etc
DEFINITION:
Vaccines are biological preparations that provides active acquired immunity to a
particular disease.
Vaccine typically contains a disease causing microorganism.
It is often made from weakened or killed forms of the causative microbes or its toxins or
one of its surface proteins.
The agent or product through which immunization is active are called immunization
agents.
Vaccines may be single component or mixed component vaccines.
ADVANTAGES:
1. No disease-transmission risk .
2. No auto immunogenic or anaphylaxis.
3. Broadly applicable with almost all important drugs (anticancer drugs , proteins, peptides,
nucleic acids , antibiotics, fungicides).
4. Enables drug delivery into the cytoplasm of target cell.
5. Protects drugs against degradation.
DISADVANTAGES:
1. Shelf-life is too short.
2. Scale up related problems.
3. Poor quality of raw material.
TYPES OF VACCINES:
Rickettsial Typhus
Toxoids Diphtheria
Tetanus
MECHANISM OF VACCINE:
UPTAKE OF ANTIGENS:
The components of the disease-causing organisms or the vaccine components that trigger
the immune response are known as “antigens”.
These antigens trigger the production of “antibodies” by the immune system. Antibodies
bind to corresponding antigens and induce their destruction by other immune cells.
The induced immune response to either a disease-causing organism or to a vaccine
configures the body’s immune cells to be capable of quickly recognizing, reacting to, and
subduing the relevant disease-causing organism.
When the body’s immune system is subsequently exposed to a same disease-causing
organism, the immune system will contain and eliminate the infection before it can cause
harm to the body.
UPTAKE
Access of native antigens and pathogens to intracellular pathways of degradation
DEGRADATION
Limited proteolysis of antigens to peptides
ANTIGEN-MHC COMPLEX FORMATION
Loading of peptides onto MHC molecules
ANTIGEN PRESENTATION
Transport and expression of peptide-MHC complexes on the surface of cells for recognition
by T cells.
What is MHC ?
The major histocompatibility complex (MHC) is a set of cell surface proteins that are
essential for the acquired immune system to recognize foreign molecules in
vertebrates, which in turn determines histocompatibility.
The main function of MHC molecules is to bind to antigens derived from pathogens
and display them on the cell surface for recognition by the appropriate T cells.
UPTAKE
Antigens/pathogens already present in cell
DEGRADATION
Antigens synthesised in the cytoplasm undergo limited proteolytic degradation in the cytoplasm
ANTIGEN-MHC COMPLEX FORMATION
Loading of peptide antigens onto MHC class I molecules
is different to the loading of MHC class II molecules
PRESENTATION
Transport and expression of antigen-MHC complexes on the surface of cells for recognition by T
cells
Particulate adjuvants.
They form very small particles that can stimulate the immune system and also enhances the
delivery of antigen to immune cells.
Examples of particulate adjuvants are:
(1) ALUM
Most commonly used adjuvant.
Consists of Aluminum salts that are not soluble in water.
Recently it is used in vaccines for Hepatitis B.
Mechanism is unknown for how it stimulates vaccine induced immunity.
(2) VIROSOMES
They are resemble to viruses but non-infectious.
They are included in Flu vaccine and Hepatitis A vaccine in Europe.
Virosomes that are incorporated in these vaccines have antigens and other proteins on
their surface, but they can not cause infection because it does not contain any genetic
material.
Mechanism: some immune cells recognize these particulate cells and engulf them and
present them to immune system and mount protective response.
(3) CYTOKINES
They are small proteins that serves as chemical messenger of the immune system.
Because of their role in immune responses, some cytokines have been evaluated as
vaccine adjuvants.
Sometimes these adjuvants are used in combinations for producing proportional immune
responses.
Depending on the chemical properties, water-soluble antigens (proteins, peptides, nucleic acids,
carbohydrates, haptens) are entrapped within the aqueous inner space of liposomes.
Lipophilic compounds (lipopeptides, antigens, adjuvants, linker molecules) are intercalated into
the lipid bilayer.
Antigens or adjuvants can be attached to the liposome surface either by adsorption or stable
chemical linking.
Advantages: Easy surface modification
Synthesized from non-toxic material
Wide range of antigen encapsulation
Plasticity
Disadvantages: Stability problem
Low antigen loading. Nanoparticle
(4) Virosomes
A virosome is a drug or vaccine delivery mechanism consisting of unilamellar
phospholipid membrane ~150mm (either a mono or bi-layer) vesicle incorporating virus
delivered proteins to allow the virosomes to fuse with target cells.
These proteins enable the virosome membranes to fuse with cells of the immune system
and thus deliver the specific antigens directly to their target cells.
They elicit a specific immune response even with weak immunogenic antigens.
Once they have delivered the antigens, the virosomes are completely degraded within the
cells.
A viral protein attached on the phospholipid bilayer not only confers structural stability
and homogeneity to virosomal formulations, which are clearly distinct from other
liposomal carrier systems.
Virosomes represent vesicular systems into which antigens can be loaded into virosomes
or adsorbed onto the virosomal surface through hydrophobic interactions.
(5) Melt in mouth strips
Quick dissolving films containing immunogens.
Melts into liquid that children and infants will swallow easily.
First designed by undergraduate students at johns Hopkins university on biomedical
engineering design day for protection against ROTA virus infection.
ROTA virus is a common cause of severe diarrhea and vomiting in children, leading to
about 600000 deaths annually. ROTA virus vaccine at present is available in a liquid or
freeze-dried form that must be chilled for transport and storage, making it very expensive
for use in impoverished areas.
In addition, newborns sometimes spit out the liquid, a problem that is less likely to occur
with a strip that sticks to and dissolves on the tongue in less than a minute.
Advantages.
1. Powder injectors offer advantages over liquids in terms of formulation and stability issues.
2. Initial safety studies suggest that the powder injectors are reasonably well tolerated, and the
particle bombardment offers advantages with regard to Langerhans cell targeting and immune
system activation.
Limitations
Research area for the permeation enhancement of small molecules for vaccine development is
very limited due to the stability considerations with these systems.
(A) Electroporation
Electroporation involves the administration of electrical pulses to create transient pores in
the skin and thus increase the skin permeability to drugs and macromolecules.
INOVIO Biomedical Corporation has developed a series of hand-held, cordless
electroporation devices that have been used in vaccine delivery studies
Delivery of DNA vaccines into muscle or skin tissue with electroporation systems
generated robust immune responses.
(B) Ultrasound or sonophoresis
Low frequency sonophoresis involves application of ultrasound waves at frequencies
between 20 to 100 kHz to the skin surface to reduce the stratum corneum barrier and
thereby increase skin permeability.
Pretreatment is given prior to the application of a drug solution or patch.
Low frequency ultrasound (20 kHz) was used to deliver a tetanus toxoid, eliciting a
robust immune response in mice to mice.
A commercial ultrasound device, SONOPREP, for administration of local anesthetic, was
launched in 2004 but withdrawn in 2007.
(D) Microneedles
Microneedles consists of pointed micro-sized projections, fabricated into arrays with up
to a hundred needles, that penetrate through the stratum corneum to create microscopic
holes, thus providing delivery pathways for vaccines and drugs.