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VACCINE DRUG DELIVERY SYSTEM
Prepared by:-Sakshi Singh
M.Pharm 1st Sem

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Contents
• Introduction
• History of vaccine
• Mechanism of vaccine
• Types of vaccines
• Uptake of antigens
• Single shot vaccines
• Mucosal vaccine delivery system
• Transdermal vaccine delivery system
• Conclusion
• References 2

3.
Drug Delivery System
• Drug delivery systems describe technologies that
carry drugs into or throughout the body. These
technologies include the method of delivery, such as
a pill that you swallow, syrups or a vaccine that is
injected.
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Figure no:1 DDS

4.
What Is Vaccine?
• Vaccines are biological preparation which provide
active acquired immunity against particular diseases.
• Vaccine word is derived from Latin word “Variolae
vaccinea” (cowpox).
• It is made of disease causing microbes, which are killed
or present in attenuated form or it’s toxins or one of it’s
surface proteins.
• It stimulates the body immune system against the
microbe and destroy it.
• The administration of vaccine is called vaccination.
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Figure no: 2 Vaccine MOA

5.
History of Vaccine
• Edward Jenner developed 1st vaccine against small pox at
1798 from cowpox.
• Louis pasture developed live attenuated cholera vaccine and
inactivated anthrax vaccine in 1897 and 1904 respectively.
• In 1923, Alexander Glenny introduce a method to inactivate
tetanus toxins, this method was used to developed diphtheria
vaccine in 1926.
• Viral tissue culture method was developed in 1950-1985,
which helped in development of inactivated and live
attenuated polio vaccines.
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Edward Jenner Louis Pasture

6.
Important Terminologies
• Antibody: A protein found in the blood that is produced in response to foreign substances (e.g.
bacteria or viruses) invading the body. Antibodies protect the body from disease by binding to
these organisms and destroying them.
• Antigens: Foreign substances (e.g. bacteria or viruses) in the body that are capable of causing
disease. The presence of antigens in the body triggers an immune response.
• Antitoxin: A solution of antibodies against a toxin. Antitoxin can be derived from either human
(e.g., tetanus immune globulin) or animal (usually equine) sources (e.g., diphtheria and botulism
antitoxin). Antitoxins are used to confer passive immunity and for treatment.
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• Active immunity: The production of antibodies against a specific disease by the immune
system. Active immunity can be acquired in two ways, either by contracting the disease
or through vaccination. Active immunity is usually permanent, meaning an individual is
protected from the disease for the duration of their lives.
• Passive immunity: Protection against disease through antibodies produced by another
human being or animal. Passive immunity is effective, but protection is generally limited
and diminishes over time (usually a few weeks or months).

8.
Mechanism of Vaccines
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Figure no: 3 Figure no: 4

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Types of Vaccines
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Figure no: 5 Vaccine Types

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Live attenuated Vaccines
• Live attenuated vaccines contain whole bacteria or
viruses which have been “weakened”(attenuated) so that
they create a protective immune response but do not
cause disease in healthy people.
• For most modern vaccines this “weakening” is achieved
through genetic modification of the pathogens.
• E.g. BCG vaccine, MMR vaccine, chickenpox vaccine.
Figure no: 6 MOA of live
attenuated vaccine

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 Inactivated Vaccines
• Inactivated vaccines contain whole bacteria or
viruses which have been killed or have been altered,
so that they cannot replicate.
• Because inactivated vaccines do not contain any live
bacteria or viruses, they cannot cause the diseases
against which they protect, even in people with
severely weakened immune systems.
• However, inactivated vaccines do not always create
such a strong or long- lasting immune response as
live attenuated vaccines.
• E.g. Rabies vaccine, Japanese encephalitis vaccine,
Inactivated polio virus (IPV) and ect.
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Figure no: 7 MOA of
inactivated vaccines

12.
 Subunit Vaccines
• Subunit vaccines which do not contain any
whole bacteria or viruses at all. Instead, these
vaccines typically contain one or more specific
antigens (or “flags”) from the surface of the
pathogen.
• The advantage of subunit vaccines over whole
pathogen vaccines is that the immune response
can focus on a small number of antigen targets
(“flags”).
• They usually require repeated doses initially and
subsequent booster doses in subsequent years.
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Figure no: 8 MOA of
subunit vaccines

13.
 Recombinant Protein Vaccines
• Recombinant vaccines are made using bacterial
or yeast cells to manufacture the vaccine. A small
piece of DNA is taken from the virus or bacterium
against which we want to protect and inserted into
the manufacturing cells.
• For example, to make the hepatitis B vaccine,
part of the DNA from the hepatitis B virus is
inserted into the DNA of yeast cells.
• These yeast cells are then able to produce one of
the surface proteins from the hepatitis B virus, and
this is purified and used as the active ingredient in
the vaccine.
• E.g. Hepatitis B vaccine, HPV (Human
Papilloma virus Vaccine), and etc..
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Figure no: 9 MOA of
recombinant vaccines
Figure no: 10 Formation
of recombinant vaccines

14.
 Toxoid Vaccines
• Some bacteria release toxins (poisonous
proteins) when they attack the body, and it is the
toxins rather than the bacteria itself that we want
to be protected against.
• The immune system recognizes these toxins and
are able to mount an immune response to them.
• Some vaccines are made with inactivated
versions of these toxins. They are called
‘toxoids’ because they look like toxins but are
not poisonous. They trigger a strong immune
response.
• E.g. Diphtheria vaccine, Tetanus vaccine, and
Pertussis (whooping cough) vaccine.
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Figure no: 11 MOA of
toxoid vaccines

15.
 RNA vaccines
• RNA vaccines use mRNA (messenger RNA) inside
a lipid membrane. This lipid membrane protects the
mRNA when it first enters the body, and also helps
it to get inside cells by fusing with the cell
membrane.
• Once the mRNA is inside the cell, machinery inside
the cell translates it into the antigen protein.
• This mRNA typically stimulate an immune
response. It is then naturally broken down and
removed by the body.
• RNA vaccines are not capable of combining with
the human genetic code (DNA).
• E.g. COVID-19 vaccine (Moderna and Pfizer)
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Figure no: 12 MOA of
RNA vaccines

16.
 Viral vector vaccine
• A viral vector vaccine is a vaccine that uses a viral vector to
deliver genetic material (mRNA) coding for a desired antigen
into the recipient's host cells. As of April 2021, six viral
vector vaccines have been authorized for use in humans in at
least one country: four COVID-19 vaccines and two Ebola
vaccines.
• Viral vector vaccines use a modified version of one virus as a
vector to deliver to a cell a nucleic acid coding for an antigen
for another infectious agent. Viral vector vaccines do not
cause infection with either the virus used as the vector, or the
source of the antigen. The genetic material it delivers does
not integrate into a person's genome.
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Figure no: 13 Viral
Vector Vaccines Types

17.
Uptake of Antigen
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Figure no: 14 Antigen Uptake

18.
Endogenous Antigen Uptake
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Figure no: 15 Endogenous uptake pathway

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Immune cells use this pathway when the virus enters the cell or a cell starts secreting defective proteins (tumor
cells).
• The viral protein or cellular defective protein is proteolytically processed into small fragments via a
complex called “Proteozome” which acts as a shredder.
• Now, the ribosome attached to ER will start producing proteins required for the synthesis of the MHC class
1 molecule.
• The further process is a little different from the exogenous pathway. Here, the antigenic peptide fragments
enter the ER and bind to MHC complex binding site.
• They enter ER through a channel called TAP 1 and TAP 2 where TAP stands for Transporter associated with
Antigen Processing.
• After the formation of the MHC + peptide complex, it is packed into vesicles.
• This vesicle then fuses with the plasma membrane and the MHC + antigen complex binds to the plasma
membrane.
• Now, the CD8 T lymphocyte can come and bind to the processed and presented antigen complex.

20.
Exogenous Antigen Uptake
• Exogenous antigens are derived from proteins produced
outside the cell. These includes various bacterial, viral,
protozoal, fungal and parasitic antigens which are
derived from outside the body.
• Exogenous antigens associate with Class II MHC
molecules that activate helper CD4+ T cells for
providing help to B and Tc cells. Exogenous antigens
are processed and presented by APCs (Antigen
Presenting Cells).
• MHC (Major Histocompatibility Complex) Molecule-
They are cell surface proteins, essential for recognizing
the foreign substance and also help to get acquired
immune system. There main function is to bind with
antigens of pathogens and expose them on cell surface,
in order to get them killed by T cells.
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Figure no: 16 Exogeneous
uptake pathway

21.
Single Shot Vaccines
• Single shot vaccine is a combination product of
a prime component antigen with an adjuvant
and a microsphere component which
encapsulates the antigen, which will provide
the booster immunization by
delayed/controlled release of the antigen.
• It is given at a single contact point for
preventing 4-6 disease. They can replace the
separate booster dose of vaccine.
• E.g. COVID-19 vaccine by Johnson & Johnson
company, Single-shot Subunit Vaccine for HIV 21
Figure no: 17 Mfg. of
single shot vaccine

22.
Mucosal Delivery Of Vaccine
• 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.
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Design And Strategies For Mucosal Delivery
• Emulsion type delivery
• Liposome based delivery
• Polymeric nano particles
• Virosomes
• Melt in mouth strips
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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.
ADVANTAGES:
• Slow release of antigen.
DISADVANTAGES:
• Access immunogenic response
• Fever
• Sore arm at injection site. 24

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Liposome Based Delivery
• Liposomes are spherical shape vesicles containing
an aqueous core which is enclosed by a lipid
bilayer.
ADVANTAGES:
• Easy surface modification.
• Plasticity
• Synthesized from non toxic material.
• Wide range of antigen encapsulation.
DISADVANTAGES:
• Stability problem.
• Low antigen loading. 25
Figure no: 18
Liposomes

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Polymeric Nanoparticles
• Polymeric nanoparticles are submicron sized
colloidal particles.
• 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.
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Figure no:19 Polymeric
Nanoparticle Formulation

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ADVANTAGES:
Release antigen at target site.
Surface properties can be easily tailored for better immunogenecity.
DISADVANTAGES:
Insufficient antigen protection.
Premature (burst) release.

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Melt In Mouth Strips
• Quick dissolving films containing immunogens.
• Melts into liquid that children and infants will
swallow easily.
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Figure no: 20 Melt In
Mouth Strips

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Transdermal Delivery of Vaccines
• Transdermal delivery is one of the needle free method of vaccine delivery.
• Transdermal delivery targets the vaccine to the skin, thereby promoting its contact and potentially
reduce the required dose of vaccine.
• It has the potential to
Reduce the risk of needle borne disease.
Improve access to vaccination by simplified procedures.
The various approaches are:
 Liquid jet injection
 Epidermal powder immunization
 Topical application.
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Figure no: 21 Various Approaches of
Transdermal Delivery Of Vaccines

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Liquid Jet Injection
• Liquid jet injectors use A HIGH- VELOCITY JET (typically 100 to 200 m/s) to deliver molecules
through the skin into the subcutaneous or intramuscular region.
• Jet injectors can be broadly divided into Multi-use nozzle jet injectors (MUNJIs) and Disposable
cartridge jet injectors (DCJIs), depending on the number of injections carried out with a single
device.
• Liquid jet injectors consists of a power source (compressed gas or spring), piston, vaccine- loaded
compartment and an application nozzle (orifice size in the range of 150 to 300 µm)
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Needle Free Injection Devices
Figure no: 24 Construction
of needle free injection
Figure no: 23 Needle And
Needle Free Injection

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ADVANTAGES:
• Increase immune responses when compared to conventional vaccine.
• Dose sparing
• Increases the speed
• Avoids risks and discomfort.
DISADVANTAGES:
• Variable reactions including pain and bruising at the site of administration.

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Epidermal Powder Immunization
• Powder injectors has been investigated for transdermal protein delivery, gene therapy and
vaccination.
• The device design principles are similar to liquid injectors, with a powder compartment and
compressed carrier gas such as Helium.
• Upon actuation, the particles are carried by the gas, to impact the skin surface at high velocity,
puncturing micron-sized holes in the epidermis to facilitate skin deposition.
• Humoral and cell mediated immune response following vaccination with jet propelled particles
has been demonstrated in clinical studies.
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Figure no: 25 Powder Injector

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Topical Application
 Topical applications range from
Non-invasive formulation based approaches (e.g. Colloidal carriers),
Energy based approaches (ultrasound or sonophoresis, and electroporation),
Minimally invasive approaches (such as microneedles)
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1.Colloidal Carriers
• The rationale for the use of colloidal carriers is that compounds with unfavourable permeation
characteristics can be packaged within carriers that will permeate the skin.
• While there has been considerable research in the application of liposomes and lipid particle
carriers, there is no conclusive evidence that these carriers can permeate the skin intact.
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2.Energy Based Approaches
• Exposure of skin to energy in form of electrical pulses or ultrasonic waves increases the
permeability of the skin.
A)ELECTROPORATION
• It involves the administration of electrical pulses to create transient pores in the skin and thus
increases the skin permeability to vaccines.
• Eg: Delivery of DNA vaccines involves electroporation.
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B )SONOPHORESIS:
Ultrasound or sonophoresis:
Application of ultraviolet waves at frequencies between 20 to 100 kHz to the skin surface increases
the skin permeability.
Eg. Tetanus toxoid.
C) MICRONEEDLES:
It consist of pointed micro sized projections fabricated into arrays upto 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:
 Poke and patch method
 Coat and poke method
 Poke and release method
 Poke and flow method

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Figure no: 26 Poke And Patch Method Figure no: 27 Coat And Poke Method

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Figure no: 28 Poke And Release Method Figure no: 29 Poke And Flow Method

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Types Of Vaccines For COVID-19
• There are a wide range of approaches being used to develop vaccines against the SARS-CoV-2
virus, which causes COVID-19. There are four COVID-19 vaccines currently approved and in
use in the UK and available via vaccination services.
• The Pfizer/BioNTech vaccine and the Moderna vaccine, which are both mRNA vaccines, the
AstraZeneca/Oxford vaccine, which is a viral vector vaccine, and the Novavax vaccine, which is
a protein vaccine.
• The Janssen vaccine for COVID-19, which is a viral vector vaccine, has also been approved in
the UK but is not currently being used in the vaccination programme. The Valneva vaccine for
COVID-19, which is an inactivated protein-based vaccine has also been approved in the UK but
is not currently being used in the vaccination programme.
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Conclusion
• Vaccines are one of the most effective health interventions ever developed for several diseases,
research is still in progress to develop vaccines for life threatening diseases like cancer ,AIDS etc.
Some boosters(adjuvants) are also used in association with vaccines for increasing the immune
response.
• Hence vaccine drug delivery system is a leading trend in health care system.
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44.
References
1. N.K.Jain “Controlled and Novel drug delivery” pg.no: 147- 164.
2. A.K.M Salman Haque “A Review on Transdermal delivery of vaccines”.
3. CH Saroja, PK Lakshmi, Shyamala Bhaskaran “Recent trends in vaccine delivery system: A review”
International Journal of Pharmaceutical Investigation | April 2011 | Vol 1 | Issue 2.
4. Review on Technological Approaches for Improving Vaccination Compliance and Coverage, Vaccines
2020, 8, 304; doi:10.3390/vaccines8020304.
5. Singh.M, Dwivedi.D, Pandey.S and Verma.M “A Review on vaccine delivery systems”.
6. Sarika Namjoshi and Heather A.E. Benson “Transdermal delivery of vaccines” Research gate.
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