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TOPIC–VACCINE DELIVERY
SYSTEMS
MADE BY
SAURABH PUNIA
M-PHARM 1ST YEAR
SCHOOL OF PHARMACEUTICAL SCIENCES
CSJMU,KANPUR
UNDER THE GUIDANCE OF
DR. ANUPRIYA KAPOOR
ASSISTANT PROFESSOR 1
What is vaccine?
• A vaccine is a biological preparation that improves or provides active
acquired immunity to a particular diseases which may be viral or
infectious.
• A vaccines typically contains an agent that resembles a disease causing
microorganism and is often made from weak or killed forms of the
microbe.
2
Cont…
• The agent stimulates the body immune system to recognise the agent
is foreign , destroy it, and keep a record of it.
• So ,that the immune system can more easily recognise and destroy any
of these microorganism that it later encounters.
• The term vaccines and vaccination are derived from variolae vaccinae
the term derived by Edward jenner denote cowpox .
3
TYPES OF VACCINES
• Live attenuated vaccine
• Inactivated or killed vaccine
• Subunit vaccine
• Toxoid vaccine
• Conjugate vaccine
• DNA vaccine
• Recombinant vaccine
4
1. LIVE ATTENUATED VACCINES
• It contains a version of the living microbes that has been weakened in
the lab so it can’t cause disease
• Because a live attenuated vaccine is the closest thing to a natural
infection these vaccines are good teachers of the immune system
• Examples- vaccines against measles mumps (MMR Vaccine) and
chickenpox (Varicella Vaccine).
5
2. INACTIVATED OR KILLED VACCINES
• Scientists produce inactivated vaccines by killing the disease microbe
with chemicals, heat or radiation. Such vaccines are more stable and
safer than live vaccines
• Because dead microbes cant mutate back to their disease causing state.
• Example- vaccine against influenza (Afluria Quadrivalent Vaccine),
polio ( IPV), hepatitis A and rabies ( ARV Vaccine)
6
3. SUBUNITS VACCINES
• Instead of the entire microbe, subunit vaccine include only the
antigens that best stimulate the immune system is used.
• In some cases these vaccines use epitopes the very specific parts of the
antigens that antibodies or t-cells recognise and bind them
• Because subunit vaccine contains only the essential antigens and not
all the other molecules that make up the microbe
• Example- plague immunization
7
4. TOXOID VACCINES
• For bacteria that secretes toxins or harmful chemicals , a toxoid
vaccine might be the answer
• The type of vaccines are used when a bacteria toxin is the main cause
of illness
• Scientists have found that they can inactivate toxins by treating them
with formalin, such detoxified toxins called toxoids are safe for use in
vaccines
• Example- crotalus atrox toxoid is used to vaccinate dogs against
rattlesnake bites
8
5. CONJUGATE VACCINES
• If a bacterium possesses an outer coating of sugar molecule called
polysaccharide , as many harmful bacteria do, researchers may try
making conjugate vaccine for it.
• Polysaccharides coatings distinguish a bacterium , antigens so, that
the immature immune systems of infants and younger children cant
recognise or respond to them
• Example- haemophilus influenzae type b vaccines
9
6. DNA VACCINES
• Still in the experimental stages, these vaccines show great promise and
several types are being tested in humans.
• Dna vaccines take immuniazation to a new technological level
• These vaccines dispense with both the whole organism and its parts
and get right down to the essentials ; the microbes genetic material
• Example- influenzae vaccine
10
7. RECOMBINANT VECTOR VACCINES
• Recombinant vector vaccines are experimental vaccine similar to Dna
vaccines
• But the use as attenuated virus or bacterium to introduce microbial
DNA to cells of the body
• Vector refers to the virus or bacterium used as the carries
• Example- DPT Vaccines
11
Research and development
• Who have separate unit for research and development of vaccines
• Who initiative for vaccine research (IVR) facilitates vaccines research
and development against pathogens with significant disease and
economic burden with a particular focus on low and middle income
countries
• Finding a safe effective and durable HIV vaccine remains a top
priority for world
12
• A substance that enters into the body and starts a process that can
cause disease is known as antigen. The body then usually produces
substances (antibodies) to fight the antigens.
• It may be –
• Exogeneous – virus, bacteria
• Endogeneous- cancer cells
ANTIGEN
13
UPTAKE OF ANTIGENS
14
STAGES OF ANTIGEN UPTAKE
• There are mainly 4 stages which includes-
• Uptake of antigens
• Degradation of antigen to peptides
• Antigen MHC complex formation
• Antigen presentation on the surface of cell and binds to T-Cells.
15
ANTIGEN PROCESSING
• The process by which pathogens and their products are degraded to
produce antigen peptides are referred to as the phenomena of antigen
processing.
• The peptides combined with MHC complex inside the cell and further
travels to the surface of cell to display peptide fragments to T-cells.
• It is a immunological process that prepares antigens for presentation to
special cells of the immune system called T- lymphocytes. It is
considered to be the stage of antigen presentation pathways.
16
TYPES OF ANTIGEN PRESENTATION
A. ENDOGENEOUS ANTIGEN UPTAKE PATHWAY
• The antigen attaches to the target cell surface.
• Genetic material or antigenic portion enters into the cell cytoplasm
• The long chain antigenic fragment is broken down to small peptides
• The peptides are transported with the help of TAP(transporter
associated with antigen presentation)
• On RER the peptides binds with MHC to form MHC-Peptides
17
• The MHC – Peptides is engulfed by golgi bodies.
• The MHC-peptides reaches the surface of the cell by the phenomena
of exocytosis
• MHC- Peptides complex is expressed over the surface of target cells.
• The complex is recognised by T-cells.
18
• B. EXOGENEOUS ANTIGEN UPTAKE PATHWAY
• The antigen attaches to the antigen presenting cells(APC) on the
target surface
• The genetic material or proteins of the antigen enters into the cell
cytoplasm and this proteins is covered by the endosomes
• Therefore, the genetic material or proteins or antigen fragments are
broken don into peptides by lysosomes
• The peptides are transported with the help of TAP to the RER.
19
• On RER the peptides binds with MHC complex peptide
• Then, MHC complex is engulfed by the golgibodies and reaches the
surface of the cell by the process of exocytosis
• The MHC complex is expressed over the surface of target cells where
the complex is recognised by the T-cells and destruction occurs
20
SINGLE SHOT VACCINES
• The single-shot vaccine is a combination product of a prime
component—antigen with an appropriate adjuvant—and a
microsphere component that encapsulates antigen and provides the
booster immunizations by delayed release of the antigen . Many
aspects need to be taken into consideration when developing such
controlled release technology-based vaccines
21
Formulation and Manufacturing of Single-
Shot Vaccines
• THERE ARE 3 THINGS WHICH WILL WE NEED TO
DEVELOP SINGLE SHOT VACCINES i.e –
• Antigen
• Adjuvants( helps to bind antigen on surface)
• Microspheres
• Antigen will be present in 2 forms i.e
Free form
Microspheres
22
23
• Important factors in the manufacture of a microsphere-based vaccine
are high encapsulation efficiency and a consistent particle production
process.
• Dex-HEMA( Dextran hydroxyethyl methacrylate) has been shown to
be very suitable for the formation of the hydrogel that facilitates
controlled release of encapsulated proteins.
• A microsphere formulation process has been developed based on this
polymer In this process, an emulsion of aqueous dex-HEMA solution
is formed in an aqueous polyethylene glycol (PEG) solution, by
mixing them in a bioreactor vessel To ensure consistently high
encapsulation efficiencies, the protein to be encapsulated is added to
the dex-HEMA solution before adding the PEG solution.
24
MUCOSAL DELIVERY SYSTEM
• Delivery of vaccines via the mucosal routes can allow antigens to
interact with the mucosa-associated lymphoid tissue (MALT) to
induce both mucosal and systemic immunity
• Mucosal vaccination is highly appealing, especially for the pediatric
population. However, vaccine delivery across mucosal surfaces is
challenging because of the different barriers that naturally exist at the
various mucosal surfaces to keep the pathogens out. There have been
significant developments in delivery systems for mucosal vaccination.
25
ROUTES OF MUCOSAL VACCINE-
26
• Majority of the pathogens invade via the mucosal surfaces such as those of the
respiratory, reproductive and the gastrointestinal tracts. This is because these
surfaces come in direct contact with the air, water, food, and the environment,
and thus form an opportunistic portal for bacterial and viral infections. The
delivery of vaccines across mucosal surfaces has the potential to stimulate
synthesis of pathogen-specific mucosal immune responses , but the conventional
systemic delivery of vaccines against infectious diseases using a needle and
syringe is unable to induce a strong mucosal immune response. Mucosal
immune responses are important because the pathogen-specific antibodies that
are stimulated by mucosal vaccination get secreted into the mucus where they
can neutralize the pathogens even before they can cause infection. Thus, success
in generating this first-line of defense on the mucosal surfaces will represent a
major advance in vaccinology, and has the potential to improve childhood
vaccinations and reduce mortality. Furthermore, delivery of vaccines to mucosal
surfaces can also induce systemic immunity similar to that induced by the
conventional needle and syringe based vaccination.
27
Mucosal vaccines licensed for human use
Disease (example of licensed
vaccine)
Delivery route Live or Inactivated
Cholera (Dukoral®, Shanchol™, and
mORC-Vax™)
Oral Inactivated
Influenza (FluMist™) Intranasal Live attenuated
Poliomyelitis (Biopolio™ B1/3, and
other oral polio vaccines - OPVs)
Oral Live attenuated
Rotavirus (Rotarix® and RotaTeq®) Oral Live attenuated
Typhoid (Vivotif®) Oral Live attenuated
28
REFERENCES
S.P. Vyas, R.K, Khar. Targeted and Controlled Drug Delivery: Novel
Carrier Systems. CBS Publishers, New Delhi, 2002, ISBN 81-239-
0799-0.
N.K. Jain (ed). Advances in Controlled and Novel Drug Delivery.
CBS Publishers and Distributors, 2008, New Delhi, India, ISBN 81-
239-1096-7
Marian R. Neutra and Pamela A. Kozlowski , “A Review article on
mucosal vaccines: the promise and the challenge”.
29
THANKYOU
30

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VACCINES DELIVERY SYSTEM

  • 1. TOPIC–VACCINE DELIVERY SYSTEMS MADE BY SAURABH PUNIA M-PHARM 1ST YEAR SCHOOL OF PHARMACEUTICAL SCIENCES CSJMU,KANPUR UNDER THE GUIDANCE OF DR. ANUPRIYA KAPOOR ASSISTANT PROFESSOR 1
  • 2. What is vaccine? • A vaccine is a biological preparation that improves or provides active acquired immunity to a particular diseases which may be viral or infectious. • A vaccines typically contains an agent that resembles a disease causing microorganism and is often made from weak or killed forms of the microbe. 2
  • 3. Cont… • The agent stimulates the body immune system to recognise the agent is foreign , destroy it, and keep a record of it. • So ,that the immune system can more easily recognise and destroy any of these microorganism that it later encounters. • The term vaccines and vaccination are derived from variolae vaccinae the term derived by Edward jenner denote cowpox . 3
  • 4. TYPES OF VACCINES • Live attenuated vaccine • Inactivated or killed vaccine • Subunit vaccine • Toxoid vaccine • Conjugate vaccine • DNA vaccine • Recombinant vaccine 4
  • 5. 1. LIVE ATTENUATED VACCINES • It contains a version of the living microbes that has been weakened in the lab so it can’t cause disease • Because a live attenuated vaccine is the closest thing to a natural infection these vaccines are good teachers of the immune system • Examples- vaccines against measles mumps (MMR Vaccine) and chickenpox (Varicella Vaccine). 5
  • 6. 2. INACTIVATED OR KILLED VACCINES • Scientists produce inactivated vaccines by killing the disease microbe with chemicals, heat or radiation. Such vaccines are more stable and safer than live vaccines • Because dead microbes cant mutate back to their disease causing state. • Example- vaccine against influenza (Afluria Quadrivalent Vaccine), polio ( IPV), hepatitis A and rabies ( ARV Vaccine) 6
  • 7. 3. SUBUNITS VACCINES • Instead of the entire microbe, subunit vaccine include only the antigens that best stimulate the immune system is used. • In some cases these vaccines use epitopes the very specific parts of the antigens that antibodies or t-cells recognise and bind them • Because subunit vaccine contains only the essential antigens and not all the other molecules that make up the microbe • Example- plague immunization 7
  • 8. 4. TOXOID VACCINES • For bacteria that secretes toxins or harmful chemicals , a toxoid vaccine might be the answer • The type of vaccines are used when a bacteria toxin is the main cause of illness • Scientists have found that they can inactivate toxins by treating them with formalin, such detoxified toxins called toxoids are safe for use in vaccines • Example- crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites 8
  • 9. 5. CONJUGATE VACCINES • If a bacterium possesses an outer coating of sugar molecule called polysaccharide , as many harmful bacteria do, researchers may try making conjugate vaccine for it. • Polysaccharides coatings distinguish a bacterium , antigens so, that the immature immune systems of infants and younger children cant recognise or respond to them • Example- haemophilus influenzae type b vaccines 9
  • 10. 6. DNA VACCINES • Still in the experimental stages, these vaccines show great promise and several types are being tested in humans. • Dna vaccines take immuniazation to a new technological level • These vaccines dispense with both the whole organism and its parts and get right down to the essentials ; the microbes genetic material • Example- influenzae vaccine 10
  • 11. 7. RECOMBINANT VECTOR VACCINES • Recombinant vector vaccines are experimental vaccine similar to Dna vaccines • But the use as attenuated virus or bacterium to introduce microbial DNA to cells of the body • Vector refers to the virus or bacterium used as the carries • Example- DPT Vaccines 11
  • 12. Research and development • Who have separate unit for research and development of vaccines • Who initiative for vaccine research (IVR) facilitates vaccines research and development against pathogens with significant disease and economic burden with a particular focus on low and middle income countries • Finding a safe effective and durable HIV vaccine remains a top priority for world 12
  • 13. • A substance that enters into the body and starts a process that can cause disease is known as antigen. The body then usually produces substances (antibodies) to fight the antigens. • It may be – • Exogeneous – virus, bacteria • Endogeneous- cancer cells ANTIGEN 13
  • 15. STAGES OF ANTIGEN UPTAKE • There are mainly 4 stages which includes- • Uptake of antigens • Degradation of antigen to peptides • Antigen MHC complex formation • Antigen presentation on the surface of cell and binds to T-Cells. 15
  • 16. ANTIGEN PROCESSING • The process by which pathogens and their products are degraded to produce antigen peptides are referred to as the phenomena of antigen processing. • The peptides combined with MHC complex inside the cell and further travels to the surface of cell to display peptide fragments to T-cells. • It is a immunological process that prepares antigens for presentation to special cells of the immune system called T- lymphocytes. It is considered to be the stage of antigen presentation pathways. 16
  • 17. TYPES OF ANTIGEN PRESENTATION A. ENDOGENEOUS ANTIGEN UPTAKE PATHWAY • The antigen attaches to the target cell surface. • Genetic material or antigenic portion enters into the cell cytoplasm • The long chain antigenic fragment is broken down to small peptides • The peptides are transported with the help of TAP(transporter associated with antigen presentation) • On RER the peptides binds with MHC to form MHC-Peptides 17
  • 18. • The MHC – Peptides is engulfed by golgi bodies. • The MHC-peptides reaches the surface of the cell by the phenomena of exocytosis • MHC- Peptides complex is expressed over the surface of target cells. • The complex is recognised by T-cells. 18
  • 19. • B. EXOGENEOUS ANTIGEN UPTAKE PATHWAY • The antigen attaches to the antigen presenting cells(APC) on the target surface • The genetic material or proteins of the antigen enters into the cell cytoplasm and this proteins is covered by the endosomes • Therefore, the genetic material or proteins or antigen fragments are broken don into peptides by lysosomes • The peptides are transported with the help of TAP to the RER. 19
  • 20. • On RER the peptides binds with MHC complex peptide • Then, MHC complex is engulfed by the golgibodies and reaches the surface of the cell by the process of exocytosis • The MHC complex is expressed over the surface of target cells where the complex is recognised by the T-cells and destruction occurs 20
  • 21. SINGLE SHOT VACCINES • The single-shot vaccine is a combination product of a prime component—antigen with an appropriate adjuvant—and a microsphere component that encapsulates antigen and provides the booster immunizations by delayed release of the antigen . Many aspects need to be taken into consideration when developing such controlled release technology-based vaccines 21
  • 22. Formulation and Manufacturing of Single- Shot Vaccines • THERE ARE 3 THINGS WHICH WILL WE NEED TO DEVELOP SINGLE SHOT VACCINES i.e – • Antigen • Adjuvants( helps to bind antigen on surface) • Microspheres • Antigen will be present in 2 forms i.e Free form Microspheres 22
  • 23. 23
  • 24. • Important factors in the manufacture of a microsphere-based vaccine are high encapsulation efficiency and a consistent particle production process. • Dex-HEMA( Dextran hydroxyethyl methacrylate) has been shown to be very suitable for the formation of the hydrogel that facilitates controlled release of encapsulated proteins. • A microsphere formulation process has been developed based on this polymer In this process, an emulsion of aqueous dex-HEMA solution is formed in an aqueous polyethylene glycol (PEG) solution, by mixing them in a bioreactor vessel To ensure consistently high encapsulation efficiencies, the protein to be encapsulated is added to the dex-HEMA solution before adding the PEG solution. 24
  • 25. MUCOSAL DELIVERY SYSTEM • Delivery of vaccines via the mucosal routes can allow antigens to interact with the mucosa-associated lymphoid tissue (MALT) to induce both mucosal and systemic immunity • Mucosal vaccination is highly appealing, especially for the pediatric population. However, vaccine delivery across mucosal surfaces is challenging because of the different barriers that naturally exist at the various mucosal surfaces to keep the pathogens out. There have been significant developments in delivery systems for mucosal vaccination. 25
  • 26. ROUTES OF MUCOSAL VACCINE- 26
  • 27. • Majority of the pathogens invade via the mucosal surfaces such as those of the respiratory, reproductive and the gastrointestinal tracts. This is because these surfaces come in direct contact with the air, water, food, and the environment, and thus form an opportunistic portal for bacterial and viral infections. The delivery of vaccines across mucosal surfaces has the potential to stimulate synthesis of pathogen-specific mucosal immune responses , but the conventional systemic delivery of vaccines against infectious diseases using a needle and syringe is unable to induce a strong mucosal immune response. Mucosal immune responses are important because the pathogen-specific antibodies that are stimulated by mucosal vaccination get secreted into the mucus where they can neutralize the pathogens even before they can cause infection. Thus, success in generating this first-line of defense on the mucosal surfaces will represent a major advance in vaccinology, and has the potential to improve childhood vaccinations and reduce mortality. Furthermore, delivery of vaccines to mucosal surfaces can also induce systemic immunity similar to that induced by the conventional needle and syringe based vaccination. 27
  • 28. Mucosal vaccines licensed for human use Disease (example of licensed vaccine) Delivery route Live or Inactivated Cholera (Dukoral®, Shanchol™, and mORC-Vax™) Oral Inactivated Influenza (FluMist™) Intranasal Live attenuated Poliomyelitis (Biopolio™ B1/3, and other oral polio vaccines - OPVs) Oral Live attenuated Rotavirus (Rotarix® and RotaTeq®) Oral Live attenuated Typhoid (Vivotif®) Oral Live attenuated 28
  • 29. REFERENCES S.P. Vyas, R.K, Khar. Targeted and Controlled Drug Delivery: Novel Carrier Systems. CBS Publishers, New Delhi, 2002, ISBN 81-239- 0799-0. N.K. Jain (ed). Advances in Controlled and Novel Drug Delivery. CBS Publishers and Distributors, 2008, New Delhi, India, ISBN 81- 239-1096-7 Marian R. Neutra and Pamela A. Kozlowski , “A Review article on mucosal vaccines: the promise and the challenge”. 29