2. CONTENTS
INTRODUCTION
TYPES OF VACCINES
UPTAKE OF ANTIGENS
SINGLE SHOT VACCINES
TRANSDERMAL VACCINE DELIVERY SYSTEM
MUCOSAL VACCINE DELIVERY SYSTEM
3. INTRODUCTION
A vaccine is a biological preparation that provides active acquired
immunity to particular infectious disease.
A vaccine typically contains an agent that resembles a disease causing by
microorganism and is often made from weakened or killed forms of the
microbe . The agent stimulates the body’s immune system to recognize the
agent as a threat.
The same agent further recognize in future and destroy it.
The administration of vaccine is called vaccination.
4. The goal of vaccination is to stimulate a strong protective and long
lasting immune response to the administered antigen.
5. PROPERTIES OF AN IDEAL
VACCINE
Give lifelong immunity.
Prevent disease transmission.
Rapidly induce immunity.
Need to be Stable, cheap and safe.
Effective in all subjects( the old and very young).
Transmit maternal protection to the fetus .
6. ROUTES OF ADMINISTRATION
Deep subcutaneous or intra muscular route (most
vaccines).
Oral route ( oral BCG vaccine).
Intradermal route (BCG vaccine).
Intranasal route ( live attenuated influenza vaccine).
Scarification ( small pox vaccine).
7. COMPOSITION OF VACCINE
Vaccines consist of:
BULK ANTIGEN + OTHER FLUIDS(water or saline) +
PRESERVATIVES + ADJUVANTS.
These ensure the quality and potency of the vaccine over its shelf
life.
Vaccines are always formulated as to be safe and immunogenic
when injected to humans.
It is formulated as liquids, but may be as freeze-dried for
reconstitution immediately prior to time of injection.
8. How do vaccines work?
A Vaccine is a tiny weakened non-dangerous fragment of the
organism and includes part of the antigen
So, after get vaccinated its enough that our body can learn to build
the specific antibody
Then if the body encounters by the real antigen later as a part of real
organism , body already knows how to defeat.
9. Herd immunity
People with underlying health conditions that weaken their immune systems
(such as cancer or HIV) or who have severe allergies to some vaccine
components may not be able to get vaccinated with certain vaccines.
These people can still be protected if they live in and amongst others who are
vaccinated.
When a lot of people in a community are vaccinated the pathogen has a hard
time circulating because most of the people it encounters are immune.
So the more that others are vaccinated, the less likely people who are unable
to be protected by vaccines are at risk of even being exposed to the harmful
pathogens. This is called herd immunity.
12. TRADITIONAL VACCINES
Killed – The killed but previously virulent, microorganism that have
been destroyed with chemicals, heat, radioactivity or antibiotics.
Eg: influenza, cholera, polio.
Live, attenuated – some vaccine contain live, attenuated
microorganism. Some of the active viruses that have been cultivated
under condition that disable their virulent properties to produce a
broad immune response.
Eg: yellow fever, measles.
13. Toxoid- made from inactivated toxic compound that cause illness
rather than the microorganism.
The toxins are inactivated by treating them with formalin. Such
detoxified toxins are called toxoids.
Eg: Tetanus and Diphtheria.
Subunit – It is a protein subunit, a fragment of it can create an
immune response.
Instead of the entire microbe, subunit vaccines include only the
antigens that stimulate the immune system.
Eg: Plague immunization
14. INNOVATIVE VACCINE
Conjugate vaccine- certain bacteria have polysaccharide outer coats
that are poorly immunogenic. By linking the outer coats to the
stronger protein, the immune system able to recognise the antigen.
Eg: Haemophilus influenza type B vaccine.
Recombinant vector vaccine- by combing the physiology of the
microorganism and the DNA of the other, immunity can be created
against the disease.
Eg: DPT
15. Valence-
Monovalent: use to immunize against single antigen.
Multivalent: use to immunize against two or more microorganism.
Heterotypic- Vaccines,that are pathogens of other animals that do
not cause disease or cause mild disease in the organism being
treated.
Eg: BCG vaccine made from Mycobacterium bovis to protect
against tuberculosis.
16. UPTAKE OF ANTIGEN
ANTIGENS:
The components of the disease-causing organisms or the
vaccine components that trigger the immune response are known as
antigen.
ANTIBODIES:
These antigens trigger the production of antibodies by the immune
system. Antibodies bind to corresponding antigens and induce their
destruction by other immune cells.
17. Steps involved
The induced immune response to either a disease-causing organism
or to a vaccine makes the body’s immune cells to be capable of
quickly recognizing, reacting to, and control the relevant disease
causing organism.
When the body’s immune system is subsequently exposed to a
same disease-causing organism, the immune system will target the
antigen and eliminate the infection before it can cause harm to the
body.
18. EXOGENOUS ANTIGENS
►Exogenous antigens are derived from
proteins that enter from outside into the body.
► These includes various bacterial, viral,
protozoal, fungal and parasitic antigens
which are derived from outside the body
19. Stages of exogenous antigen uptake
i. Access or uptake of exogenous antigens and pathogens to
intracellular pathways of degradation
ii. Degradation of antigens to peptides by proteolysis
iii. Loading of peptides on major histocompatibility complex
(MHC)and form Antigen-MHC complex
iv. Then transport and expression of peptide-MHC complex on the
surface of cell for recognition by T cells
20. What is MHC?
The Major Histocompatibility Complex (MHC) is a set of cell
surface proteins that essential for the Acquired immune system to
recognize foreign molecules
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
21. ENDOGENOUS ANTIGEN
► Endogenous antigens are derived from
proteins produced inside the cell.
► These includes altered self-protein antigens
(e.g. tumor antigens) and non-self protein
antigens (e.g. viral antigens).
22. Stages of endogenous antigen uptake
i. Antigens/pathogens already present in the cell
ii. Antigens synthesized in cytoplasm undergo limited
proteolytic degradation to form peptides
iii. Formation of complex of peptide -MHC
iv. Then transport and expression of peptide-MHC complex
on the surface of cell for recognition by T cells
23. SINGLE SHOT VACCINE
In traditional vaccines are requires booster dose and repeated dose to
induced immunity. .
Single shot vaccines are given for preventing four to six diseases
with only one injection.
These disadvantages have spurred the development of single shot
vaccine that can provide protection against infection with only one
injection
24. Concepts
► The single shot vaccine is a combination product of a prime
component antigen with appropriate adjuvant and a microsphere
component.
► Adjuvants increase the therapeutic efficiency of such vaccines.
► Microsphere component that encapsulated antigen and provides the
booster immunization by delayed release of the antigen.
25. FORMULATION OF SINGLE SHORT
VACCINES
• Antigen/protein
• Vaccine adjuvants
gel types: aluminium hydroxide , calcium phosphate
oil emulsion and emulsifier based: liposomes , bio microspheres
• Biodegradable polymers
natural polymers: albumin, collagen, gelatin
synthetic bio polymer : aliphatic polyesters
26. VACCINE ADJUVANT
Adjuvant are the substances added to vaccine to help them work
better .Adding an adjuvant triggers the immune system to became
more sensitive to the vaccine.
Need for Adjuvant ;-
► To increase the therapeutic efficiency
► They form depot of antigen at site of inoculation with slow release
of antigen.
► It can improve the performance of vaccines by targeting the antigen
to APC
27. TRANSDERMAL VACCINE
DELIVERY SYSTEM
► INTRODUCTION:
The transdermal drug delivery system is a technique that provides
drug absorption via the skin. Skin is known to be the highly
immunogenic site for vaccination.
Transdermal delivery is one of
the needle free method of vaccine
delivery.
28. NEEDLE-FREE DELIVERY
► Needle-free technology (Jet injectors), were developed in the 1930s
and used extensively over 50 yr in mass vaccination programs in
people for smallpox, polio, and measles.
29. JET INJECTORS
Jet injector uses either spring mechanism or it consist of pressurized
gases in a small cartridge or large canister form to force the
aerosolized drug into the solution or through
the skin either directly into the muscle or
into the subcutaneous or intradermal layers.
A high enough pressure can be generated by
a fluid in intimate contact with the skin, then
the liquid will punch a hole in to the skin and
be delivered in to the tissues
30. MECHANISM OF JET INJECTOR
► It consist of a power source (compressed gas or spring), piston,
drug-loaded compartment and a nozzle with orifice size typically
ranging between 150 and 300microns.
► Upon triggering the actuation mechanism, the power source pushes
the piston.
► there by leading to a quick increase in pressure.
► This forces the drug solution through the nozzle orifice as a liquid
jet with velocity ranging between 100 and 200m/s.
31. MICRONEEDLES
It consist of pointed micro sized projections fabricated into arrays up
to hundred needles to penetrate the skin surface thereby allow the
vaccine delivery.
It is made of titanium or silicone.
There are several approaches for the delivery of vaccines by the
microneedles namely:
i. Poke and patch method
ii. Coat and poke method
iii. Poke and release method
iv. Poke and flow method
32. 1.Poke and patch method
The microneedle permeabilize the skin by forming micro sized holes
through the stratum corneum.
Then the microneedle array is removed and then the vaccine
containing patch is applied.
This approach is termed as poke and patch method.
33. 2.Coat and poke method
Solid microneedles are coated with dry powder in the skin.
Coated microneedles have an insoluble core coated with dry powder
vaccine that dissolves off within the skin.
This approach is termed as “coat & poke”.
34. 3.Poke and release method
Polymer microneedles contain the vaccine in a solid solution of
needle that dissolves, swells or degrades on skin insertion, then
releases the vaccine
This approach is termed as “poke & release”.
35. 4. Poke and flow method
Hollow microneedles through which the vaccine solution can be
infused into the skin.
Insoluble hollow microneedles create holes through which the
vaccine solution can pass into the skin
This approach is termed as “poke & flow”.
36. MUCOSAL VACCINE DELIVERY
SYSTEM
Mucosal surface area is major portal of entry for many human
pathogens that are the cause of infectious disease worldwide.
Immunization by mucosal routes may be more effective at inducing
protective immunity against mucosal pathogens at their site of entry.
Discovery of safe and effective mucosal adjuvants are also being
sought to enhance the magnitude and quality of the protective
immune response.
It is estimated that 70% of infectious agents enter the host by
mucosal routes.
37. INTRANASAL VACCINE DELIVERY
Nasal administrations of vaccines have been shown to achieve a better
systemic bioavailability and protection from gastric enzymes compared
with parenteral and oral administration.
Thus increasing the general efficacy of the vaccine
Nasal immunization does not require needles and syringes
ORAL VACCINE DELIVERY
Oral vaccination is the preferred route for patients, it is easy to administer
to all ages of patient.
Oral vaccination is much easier to arrange for large-scale vaccination
programs. There are examples of oral administration of oral polio.
38. ORAL CAVITY VACCINE DELIVERY
Sublingual (SL) vaccines also lead to systemic uptake of antigens
into the bloodstream, avoiding first-pass metabolism by the liver and
facilitating a more direct stimulation of immunity.
Tablets or mucoadhesive films create there most stable vaccines that
dissolve under the tongue.
INTRA PULMONARY VACCINE DELIVERY
The lungs are a good target for vaccine administration due to their
large surface area and the presence of large numbers of antigen-
processing alveolar macrophages and dendritic cells.
There are a variety of delivery devices for achieving drug delivery to
the lungs, including inhalers and nebulizer. eg -BCG Vaccine
39. DESIGN AND STRATERGIES FOR
MUCOSAL DELIVERY
EMULSION TYPE DELIVERY
LIPOSOME BASED DELIVERY
POLYMERIC NANO PARTICLES
VIROSOMES
MELT IN MOUTH STRIPS
40. 1.Emulsion type delivery
Emulsions are heterogeneous liquid systems may be water-in-oil
emulsions(w/o) , oil in water emulsions(o/w), or more complex
systems such as water in oil in water (w/o/w) multiple emulsions,
micro emulsions, or nano emulsions.
Antigens are dissolved in a water phase and emulsified in the oil in
the presence of an appropriate emulsifier.
Eg: High oil content – injection site irritation.
Too large droplet size – physically unstable product.
41. 2.Liposome based delivery
Liposomes are spherical shape vesicles containing an aqueous core
which is enclosed by a lipid bilayer.
Depending on the chemical properties, water
soluble antigens (proteins, peptides,
nucleic acids , carbohydrates) are entrapped
within the aqueous inner space of liposomes.
Antigens or adjuvants can be attached to the
liposome surface either by adsorption or
stable chemical linking
42. 3.Polymeric nano particles
Polymeric nanoparticles are submicron sized colloidal particles.
Polymeric nanoparticles because of their size are preferentially taken
up by the mucosa associated lymphoid tissue.
Limited doses of antigen are sufficient to induce effective
immunization.
Hence, the use of nanoparticles for oral delivery of antigens is
suitable because of their ability to release proteins and to protect
them from enzymatic degradation in the gut.
43. Biodegradable Poly Methyl Metha Acrylate (PMMA) nanoparticles
being very slowly degradable ( 30% - 40% per year) appears to be
particularly suitable for vaccine purpose because prolonged contact
between antigen and immunocompetent cells favours persistent
immunity.
44. 4.Virosomes
A virosome is a drug or vaccine delivery mechanism consisting of
unilamellar phospholipid membrane of 150 mm (either mono or
bilayer) vesicle incorporating virus derived 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.
45. Once they have delivered the antigens, the virosomes are completely
degraded within the cells.
Virosomes represent vesicular systems into which antigens can be
loaded into virosomes or adsorbed onto the virosomal surface
through hydrophobic interactions.
46. 5.Melt in mouth strips
Quick dissolving films containing immunogens/antigens.
Melts into liquid that children and infants will swallow easily.
The strips stick and dissolves on the tongue in less than a minute
Eg: Rotavirus vaccine is available in mouth strips.