Presentation on the vaccine delivery system. topic included by PCI to the master's course in Pharmaceutics.

1. Guided by
Dr. Sayyad F. J.
(HOD, Department of Pharmaceutics)
Presented by
Somani R. M.
(M.Pharm F. Y.)

2. CONTENT
• Introduction
• Vaccine
• Uptake of antigens.
• single shot vaccines
• mucosal and transdermal delivery of vaccines.
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3. INTRODUCTION TO VACCINE
DELIVERY SYSTEM:-
The concept of “vaccine delivery” include a range
of devices and physical delivery systems that
are designed to allow immunization using non‐
invasive routes and to achieve different routs
of vaccine administration.
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4. VACCINES
What is a vaccine?
• The word “vaccine” originates from the Latin
Variolae vaccinae (cowpox)
• Vaccine is demonstrated by Sir. Edward Jenner in
1798 which could prevent smallpox in humans.
• These are the antigenic agents which stimulate
body's to recognize the agent as foreign, and
destroy it, and keep a record of it, so that the
immune system can more easily recognize it and
destroy any of these microorganism that it later
encounters.
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5. TYPES OF VACCINES
The different types of vaccines are as follows
1. Live, attenuated vaccine
2. Inactivated vaccine
3. Subunit vaccine
4. Toxoid vaccine
5. Conjugate vaccine
6. DNA vaccines
7. Recombinant vector vaccine
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6. UPTAKE OF ANTIGENS
Mechanism
• There is growing evidence that the different antigen
presenting cells use specialized mechanism for antigen
uptake.
• Macropinocytosis and the activity of the mannose receptor
have been identified as efficient mechanism of antigen
capture in dendritic cell.
• Mechanism of uptake determine the intercellular compartment
to which antigen is delivered and may determine the type of T-
cells epitopes generated.
• New pathways for presentation of exogenous antigen on MHC
class I and class II molecules have been identified.
• These finding provides new insights into antigen presentation
in vivo and will be instumental in designing better methods of
vaccination.
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7. DELIVERY SYSTEMS USED
TO PROMOTE UPTAKE
• Absorption enhancers
• Lipid carrier systems
• Oral immunization
• Controlled release micro particles for vaccine development
• Single dose vaccine delivery systems using bio degradable
polymers
• Peptide based vaccines
• Nucleic acid based vaccines
I DNA vaccines
II RNA vaccines
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8. ABSORPTION ENHANCERS
• The term absorption enhancer usually refers to an
agent whose function is to increase absorption by
enhancing membrane permeation, rather than
increasing solubility, so such agents are sometimes
more specifically termed as permeation enhancers.
• Skin permeation enhancers include non-ionic
surfactants which cause changes in the intracellular
proteins of stratum corneum and increase
permeability by this mechanism.
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9. LIPID CARRIER SYSTEMS
• Liposome's are concentric bilayered vesicles in which
hydrophilic moieties are enclosed by a membranous lipid
bilayer mainly composed by natural or synthetic
phospholipids.
• Viruses, proteins, glyco proteins, nucleic acids,
carbohydrates and lipids can be entrapped and targeted
at cellular and sub cellular level.
• The development of polymerized liposome's which have
shown enhanced stability in the GIT also offers potential
for use in mucosal delivery.
• Liposomal vaccines based on viral membrane proteins
(virosomes) have been approved as products in Europe
for hepatitis A and influenza.
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10. A virosome is a drug or vaccine delivery mechanism
consisting of unilamellar phospholipid membrane (either a
mono- or bi-layer) vesicle incorporating virus derived
proteins to allow the virosomes to fuse with target cells.
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11. ORAL IMMUNIZATION
• Most currently available vaccines are delivered by
injection, which makes mass immunization more
costly and less safe, particularly in resource-poor
developing countries.
• Oral vaccines have several attractive features
compared with parenteral vaccines, but these are
regarded historically as likely to be less effective, as
vaccine antigens undergo digestion in the GI tract
prior to induction of an immune response.
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12. IMMUNE RESPONSES IN
ORAL IMMUNIZATION
• Orally delivered vaccines are processed and presented by the
digestive tract’s immune system, often referred to as the
gut-associated lymphoid tissue (GALT).
• The GALT is a complex system consisting of inductive sites
(where antigens are encountered and responses are initiated)
and effector sites (where local immune response occur) linked
by a homing system, where by cells induced by antigen in the
GALT migrate to the circulation and, subsequently colonize the
mucosa.
• As a result, oral vaccination can induce immune responses
locally in the gut and at distant mucosal sites, as well as
systemic humoral and cellular immune responses.
• Oral vaccination typically generates a large amount of
secretary IgA, which plays a major role in mucosal defense.
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13. CONTROLLED RELEASE
MICRO PARTICLES FOR
VACCINE DEVELOPMENT
• PLGA( polylactide co-glycolic acid) is used as a
biodegradable micro particle for vaccine delivery
due to the abundance of data and information on its
properties, uses and role in on going studies.
• A particular interesting area is the use of the
biodegradable micro particles is to deliver DNA
vaccines.
• These are the third generation vaccines, and are
made up of a small, circular piece of bacterial DNA
(called plasmid) that has been genetically
engineered to produce one or two specific proteins
(antigens) from a pathogen.
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14. • Mechanism of release from microspheres is by bulk
erosion process .
Factors that effect the release pattern are: –
1. Molecular weight of compound:- As greater the mol.
Wt. greater the bond strength, larger time to degrade.
2. Chemical composition of co-polymer:- Release of the
peptide was prolonged when microspheres made of
copolymer containing higher proportion of polylactide.
3. Size of the microspheres:- Greater the particle size
longer the time to collapse, delays the release of
antigen.
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15. • Microencapsulation of vaccine antigen using
biodegradable polymers seems a promising
technology for needle-free targeted vaccination.
• Malaria is a mosquito borne disease caused by a
parasite.
• Recent studies showed that upon encapsulating a
subunit malarial antigen SPf66 in PLGA- mixture
microspheres resulted in high antibody levels in
mice.
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16. SINGLE DOSE VACCINE DELIVERY
SYSTEMS USING BIO DEGRADABLE
POLYMERS
• Single dose vaccines are given at a single contact point
for preventing 4 to 6 diseases.
• They would replace the need for a prime boost regimen,
consequently eliminating the repeated visits to the
doctor’s for mother’s and their children.
• In 1988, the WHO and united Nations children’s Fund
joined forces and offered their support for clinical trial of
a single dose tetanus vaccine.
• However, due to instabilities with PLGA microparticles ,
further development was subsided.
• Another reason for the Single dose vaccine gaining
popularity was cost in comparison to the current vaccine.
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17. PEPTIDE BASED VACCINES
• A peptide vaccine is a type of subunit vaccine in which a
peptide of the original pathogen is used to immunize an
organism.
• These types of vaccines are usually rapidly degraded
once injected into the body, unless they are bound to a
carrier molecule such as a fusion protein.
• Antibodies usually bind to surface proteins of the
pathogen or proteins generated after the disruption of the
pathogen.
• Binding of antibodies to these proteins will stimulate an
immune response.
• Therefore proteins can be use to stimulate an immune
response.
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18. NUCLEIC ACID BASED
VACCINES
• The use of nucleic acid-based vaccines is a novel
approach for immunization that form immune
responses similar to those induced by live,
attenuated vaccines
• Nucleic acid vaccines have been shown to form
both antibody and cytotoxic T-lymphocytes
responses to diverse protein antigens.
• It has following advantages:
Simplicity of the vector, The ease of delivery,
Duration of expression.
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19. • Nucleic acid vaccines are still experimental, and have
been applied to a number of viral, bacterial and parasitic
models of disease as well as to several tumor models
Types of nucleic acids:
1. DNA (deoxy ribose nucleic acid)
2. RNA (ribo nucleic acid)
• Direct DNA delivery in vivo can be utilized for the
production of proteins as well as for the induction of
specific cellular and humoral immune response against a
large number of viral pathogens ( influenza, hepatitis b,
HIV, etc.)
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20. 1. DNA VACCINES
• DNA vaccination is a technique for protecting an
organism against disease by injecting it with
genetically engineered DNA to produce an
immunological response.
• These are the third generation vaccines, and are
made up of a small, circular piece of bacterial DNA
(called plasmid) that has been genetically
engineered to produce one or two specific proteins
(antigens) from a pathogen.
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21. 2. RNA VACCINES
• Recent studies have demonstrated that mRNA
formulated in liposome's and administered
subcutaneously or intravenously, effectively
generated antibody.
• However, the difficulty and expenses of large scale
RNA production and the relative instability of mRNA
compared to DNA might render RNA vaccines an
impractical means of immunization.
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22. NOVEL APPROACHES TO
VACCINE DELIVERY
• Improvements are required to enable the successful develop-
ment of vaccines against infectious diseases that have so far
proven difficult to control with conventional approaches.
• Improvements may include the addition of novel injectable
adjuvants or the use of novel routes of delivery, including
mucosal immunization.
• Mucosal delivery may be required to provide protection
against pathogens that infect at mucosal sites, Alternatively,
novel approaches to delivery,
• Mucosal administration, may be used to improve compliance
for existing vaccines. Of particular interest for safer mass
immunization campaigns are needle‐free delivery devices,
which would avoid problems due to needle, re‐use in many part
of the world and would avoid needle‐stick injuries.
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23. MUCOSAL DELIVERY OF
VACCINES
• The mucosal membrane and skin is a strong
component of the immune system.
• The three main functions of mucosal system are
(i) To protect the mucous membranes against
colonization and invasion of microbes,
(ii) To prevent uptake of undegraded antigens
including foreign proteins that are derived from
ingested food, airborne matter and commensal
microorganisms and
(iii) To prevent potentially harmful immune responses
that may occur if these antigens enter the body.
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24. • The primary reason for using a mucosal route of
vaccination is that most infections affect or start from
mucosal surfaces.
• Mucosal vaccines have currently been investigated
using a broad spectrum of nanocarrier systems such
as multiple emulsions, liposomes, polymeric
nanoparticles etc.
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25. • Transdermal immunization involves the application of vaccine
antigen and often adjuvant to the skin with subsequent
penetration to immune cells that reside in the skin.
• It has a number of attractive features including its ability to
induce both systemic and mucosal immune responses and its
safety profile.
• It is well tolerated and not at all painful, but it does commonly
lead to a mild rash at the site of immunization.
• Skin patch delivery has the potential to increase ease and
speed of vaccine administration and to decrease costs when
compared to vaccination with needle and syringe.
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TRANSDERMAL DELIVERY OF
VACCINES

26. THANK
YOU
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27. REFERENCES
• Controlled and novel drug delivary by N.K. Jain CBS publication.
• Advances In Vaccination: A Review By Swarnali Dasa*, Rohitas Deshmukh,
International Journal of Applied Pharmaceutics Vol 1 Issue 1, 2009
• Neutra MR, Kozlowski PA. Mucosal vaccines: the promise and the challenge. Nat
Rev Immunol 2006;6:148–58.
• Mucosal delivery of vaccines: a review zara sheikh*, nishat jahan, rejaul karim Zara
Sheikh*et al. /International Journal of Pharmacy & Technology
• Vaccines Wim Jiskoot Division of Drug Delivery Technology Leiden/Amsterdam
Center for Drug Research (LACDR) Leiden University The Netherlands.
• Mucosal Vaccine Design and Delivery Kim A. Woodrow,1 Kaila M. Bennett,2,3 and
David D. Lo2 The Annual Review of Biomedical Engineering is online at
bioeng.annualreviews.org
• Recent advances in vaccine delivery by Soni Khyati J., Patel Rakesh P., Asari
Vaishnavi M. and Prajapati Bhupendra G Journal of Applied Pharmaceutical Science
01 (01); 2011: 30-37
• Bernard KW., Mallonee J., Wright JC. Preexposure immunization with intradermal
human diploid cell rabies vaccine, Risks and benefits of primary and booster
vaccination. The Journal of the American Medi Asso.2005; 257(8): 1059–1063.
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