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A seminar on
Presented by
Syed Imran Syed
Usman
M Pharm sem I
Dept. of Pharmaceutics
DBCOP, Besa, Nagpur.
Guided by
Dr. N.M. Mahajan
Asst. Professor
DBCOP, Besa,
Nagpur
1
Contents….
 About vaccine
 History
 Definition
 Types
 Mechanism of uptake and transport
 Delivery system used to promote uptake
 Single shot vaccine
 Introduction
 Formulation and processing
 Release of antigen
 Factor affecting antigen release
 Future consideration
 Adverse effect, Risk associated, Recent trend, Conclusion
 References 2
Vaccine -- From the latin word vacca(cow)
 The dairy workers would never have the often
fatal disease smallpox because they already have
the cowpox.
3
Jenner took the puss from the hand of a milkmaid
with cowpox, scratched it into the arm of an 8 yr old boy
and six weeks later inoculated the body with smallpox, he
observed that boy did not catch smallpox.
4
The term vaccines and
vaccinations are derived
from variolae vaccinae
(small pox of the cow), the
term devised by Edward
Jenner to denote cow pox.
Edward Jenner Louis Pasteur
The second generation
of vaccines was introduced
in 1880 by Louis Pasteur
who developed vaccines
for chicken cholera.
5
 A vaccine is a biological preparations that improves
immunity to a particular disease.
 A vaccine typically contains an agent that resembles a
disease causing microorganism and is often made
from weakened or killed forms of the microbe, its
toxins or one of its surface proteins.
6
Vaccines are dead or inactivated organisms or
purified product derived from them. The different
types of vaccines are ;
a) Traditional vaccines
b) Innovative vaccines
7
a) Traditional vaccines
1. Killed – Some vaccines contain killed, but previously virulent,
microorganism that have been destroyed with chemicals, heat,
radioactivity or antibiotics. Examples are influenza, cholera, polio,
hepatitis A, and rabies.
2. Live, attenuated – Some vaccines contain live, attenuated
microorganisms. Many of these are active viruses that have been
cultivated under conditions that disable their virulent properties or
that use closely related but less dangerous organisms to produce a
broad immune response. Example are yellow fever, measles,
mumps.
8
3. Toxoid - Toxoid vaccines are made from inactivated toxic
compound that cause illness rather than the microorganism.
Examples are Tetanus and Diphtheria.
4. Subunit – Protein subunit –Rather than introducing an
inactivated or attenuated microorganism to an immune system (which
would constitute a whole agent vaccine), a fragment of it can create
an immune response.
9
b) Innovative vaccines
1. Conjugate vaccines- Certain bacteria
have polysaccharide outer coats that are poorly
immunogenic. By linking these outer coats to
protein(e.g. toxin), the immune system can be
led to recognize the polysaccharide as if it were
a protein antigen.
2. Recombinant vector vaccine- By
combining the physiology of one
microorganism and the DNA of the other,
immunity can be created against diseases that
have complex infection process.
10
3. T-cell receptor peptide vaccine – They show the
modulation of cytokine production and improve cell mediated
immunity and are under development.
4. Valence –
a) Monovalent- Use to immunize against single antigen.
b) Multivalent- Used to immunize against two or more
microorganism.
5. Heterotypic – Vaccines that are pathogens of other animals
that either do not cause disease or cause mild disease in the organism
being treated.
11
12
UPTAKE
Access of native antigens and pathogens to intracellular pathways
of degradation
DEGRADATION
Limited proteolysis of antigens to peptides
ANTIGEN-MHC COMPLEX
Loading of peptide onto Major histocompatibility complex class II
ANTIGEN PRESENTATION
Transport and expression of peptide-MHC complexes on the
surface of cells for recognition by T-cells .
13
14
FFFig
Fig- Exogenous antigen processing
15
UPTAKE
Antigen/pathogens already present in cell
DEGRADATION
Antigens synthesized in the cytoplasm undergo limited proteolytic
degradation in the cytoplasm.
ANTIGEN-MHC COMPLEX FORMATION
Loading of peptide antigens onto MHC class 1 molecules
PRESENTATION
Transport and expression of antigens-MHC complexes on the
surface of cells.
16
17
Fig- Endogenous antigen processing
18
Delivery system used to promote uptake….
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
sometime more specifically termed as permeation enhancers.
 Absorption enhancers are functional excipients included in
formulation to improve the absorption of a pharmacologically
active drug.
 Ex ; Skin permeation enhancer include non-ionic surfactant which
causes changes in the intracellular proteins of stratum corneum
and increase permeability by this mechanism.
19
Lipid carrier systems …..
 Liposomes are concentric bilayered vesicles in which hydrophillic
moities are enclosed by a membranous lipid bilayer mainly
composed by natural or synthetic phospholipids.
20
 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.
 To provide effective patient protection, many traditional vaccines
require multiple injections, which results in a costly and
inconvenient regimen. These disadvantages have spurred the
development of single-shot vaccines that can provide protection
against infection with only one injection.
21
22
Delayed antigen release from dex-HEMA
microspheres
 Once the freeze-dried microsphere product is rehydrated by
reconstitution in an aqueous solution, hydrolysis of the carbonate
ester groups in the dex-HEMA will be initiated.
 This will increase the mesh size in the hydrogel network. The
encapsulated protein will be released when the mesh size exceeds
the hydrodynamic diameter of the protein.
23
Factor affecting antigen release
1. Polymer nature
2. Crystallinity
3. Method of preparation
4. Molecular weight of drug
5. Carrier size and morphology
24
Future consideration for single dose vaccine
delivery
 As most vaccines in the current immunization schedule are given
as two or more discrete doses at set time intervals, combining
pulsatile delivery with the currently licensed vaccines
formulations in an attractive possibility.
 In this setting the existing vaccine in its soluble form constitutes
the prime , and the encapsulated forms acts as the boost.
 Single vaccinations that mimic multiple doses through pulsed
release of antigen should be as immunogenic as multiple dose
regime, providing that the polymer dose not alter the immune
response.
 The development of encapsulated vaccine technology with
pulsatile release could offer a realistic opportunity to replace
existing repeated immunization vaccine and significantly improve
immunization.
25
Fever
Pain around injection site
Muscle aches
26
The primary risk associated with vaccines, especially
vaccines that utilize live organisms, is that the vaccine
itself causes illness.
The vaccine may behave as a super antigen and over
stimulate the immune system.
 Some individual may have an allergic reaction to the
vaccines.
27
o Approaches for designing a preventive HIV
vaccine.
o Vaccine against Dengue.
o Malaria is mosquito born 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.
28
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. As the vaccines have
benefits, they carry some harmful effects too.
29
1. Leo De Leede, Rianne Roukema, Bas Kremer “Advances in
Single-shot Vaccine Development” Biopharm International
Volume 2009(1).
2. Aungust BJ. International permeation enhancers ,J Pharm
Sci.2000;89::429442.doi:10.1002/(SICI)15206017(200004)89:4<
429::AID-JPS 1>3.0.CO;2-J.
3. Vivek Shrivastava and U.K. Jain “Design of Single Dose Control
Release Device for Antigen Delivery based on Poly (Lactic-Co-
Glycolic Acid)” International Journal of Pharmaceutical Sciences
and Nanotechnology, Volume-3,Oct-Dec 2010.
4. Adam A. Walters, Christos Krastew, Adrian V.S. Hill and Anita
Milicic, “Next Generation Vaccines: Single-dose Encapsulated
Vaccines for Improved Global Immunization Coverage and
Efficacy” Journal of Pharmacy and Pharmacology Nov 9,2014
doi:10.1111/jphp.12367.
30
5. http://www.slideshare.net
6. http://en.m.wikipedia.org
7. http://www.youtube.com
8. http://www.google.com
Net sources
31
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34

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Vaccine introduction,antigen uptake,single shot vaccine

  • 1. A seminar on Presented by Syed Imran Syed Usman M Pharm sem I Dept. of Pharmaceutics DBCOP, Besa, Nagpur. Guided by Dr. N.M. Mahajan Asst. Professor DBCOP, Besa, Nagpur 1
  • 2. Contents….  About vaccine  History  Definition  Types  Mechanism of uptake and transport  Delivery system used to promote uptake  Single shot vaccine  Introduction  Formulation and processing  Release of antigen  Factor affecting antigen release  Future consideration  Adverse effect, Risk associated, Recent trend, Conclusion  References 2
  • 3. Vaccine -- From the latin word vacca(cow)  The dairy workers would never have the often fatal disease smallpox because they already have the cowpox. 3
  • 4. Jenner took the puss from the hand of a milkmaid with cowpox, scratched it into the arm of an 8 yr old boy and six weeks later inoculated the body with smallpox, he observed that boy did not catch smallpox. 4
  • 5. The term vaccines and vaccinations are derived from variolae vaccinae (small pox of the cow), the term devised by Edward Jenner to denote cow pox. Edward Jenner Louis Pasteur The second generation of vaccines was introduced in 1880 by Louis Pasteur who developed vaccines for chicken cholera. 5
  • 6.  A vaccine is a biological preparations that improves immunity to a particular disease.  A vaccine typically contains an agent that resembles a disease causing microorganism and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. 6
  • 7. Vaccines are dead or inactivated organisms or purified product derived from them. The different types of vaccines are ; a) Traditional vaccines b) Innovative vaccines 7
  • 8. a) Traditional vaccines 1. Killed – Some vaccines contain killed, but previously virulent, microorganism that have been destroyed with chemicals, heat, radioactivity or antibiotics. Examples are influenza, cholera, polio, hepatitis A, and rabies. 2. Live, attenuated – Some vaccines contain live, attenuated microorganisms. Many of these are active viruses that have been cultivated under conditions that disable their virulent properties or that use closely related but less dangerous organisms to produce a broad immune response. Example are yellow fever, measles, mumps. 8
  • 9. 3. Toxoid - Toxoid vaccines are made from inactivated toxic compound that cause illness rather than the microorganism. Examples are Tetanus and Diphtheria. 4. Subunit – Protein subunit –Rather than introducing an inactivated or attenuated microorganism to an immune system (which would constitute a whole agent vaccine), a fragment of it can create an immune response. 9
  • 10. b) Innovative vaccines 1. Conjugate vaccines- Certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to protein(e.g. toxin), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. 2. Recombinant vector vaccine- By combining the physiology of one microorganism and the DNA of the other, immunity can be created against diseases that have complex infection process. 10
  • 11. 3. T-cell receptor peptide vaccine – They show the modulation of cytokine production and improve cell mediated immunity and are under development. 4. Valence – a) Monovalent- Use to immunize against single antigen. b) Multivalent- Used to immunize against two or more microorganism. 5. Heterotypic – Vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. 11
  • 12. 12
  • 13. UPTAKE Access of native antigens and pathogens to intracellular pathways of degradation DEGRADATION Limited proteolysis of antigens to peptides ANTIGEN-MHC COMPLEX Loading of peptide onto Major histocompatibility complex class II ANTIGEN PRESENTATION Transport and expression of peptide-MHC complexes on the surface of cells for recognition by T-cells . 13
  • 14. 14
  • 16. UPTAKE Antigen/pathogens already present in cell DEGRADATION Antigens synthesized in the cytoplasm undergo limited proteolytic degradation in the cytoplasm. ANTIGEN-MHC COMPLEX FORMATION Loading of peptide antigens onto MHC class 1 molecules PRESENTATION Transport and expression of antigens-MHC complexes on the surface of cells. 16
  • 17. 17
  • 18. Fig- Endogenous antigen processing 18
  • 19. Delivery system used to promote uptake…. 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 sometime more specifically termed as permeation enhancers.  Absorption enhancers are functional excipients included in formulation to improve the absorption of a pharmacologically active drug.  Ex ; Skin permeation enhancer include non-ionic surfactant which causes changes in the intracellular proteins of stratum corneum and increase permeability by this mechanism. 19
  • 20. Lipid carrier systems …..  Liposomes are concentric bilayered vesicles in which hydrophillic moities are enclosed by a membranous lipid bilayer mainly composed by natural or synthetic phospholipids. 20
  • 21.  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.  To provide effective patient protection, many traditional vaccines require multiple injections, which results in a costly and inconvenient regimen. These disadvantages have spurred the development of single-shot vaccines that can provide protection against infection with only one injection. 21
  • 22. 22
  • 23. Delayed antigen release from dex-HEMA microspheres  Once the freeze-dried microsphere product is rehydrated by reconstitution in an aqueous solution, hydrolysis of the carbonate ester groups in the dex-HEMA will be initiated.  This will increase the mesh size in the hydrogel network. The encapsulated protein will be released when the mesh size exceeds the hydrodynamic diameter of the protein. 23
  • 24. Factor affecting antigen release 1. Polymer nature 2. Crystallinity 3. Method of preparation 4. Molecular weight of drug 5. Carrier size and morphology 24
  • 25. Future consideration for single dose vaccine delivery  As most vaccines in the current immunization schedule are given as two or more discrete doses at set time intervals, combining pulsatile delivery with the currently licensed vaccines formulations in an attractive possibility.  In this setting the existing vaccine in its soluble form constitutes the prime , and the encapsulated forms acts as the boost.  Single vaccinations that mimic multiple doses through pulsed release of antigen should be as immunogenic as multiple dose regime, providing that the polymer dose not alter the immune response.  The development of encapsulated vaccine technology with pulsatile release could offer a realistic opportunity to replace existing repeated immunization vaccine and significantly improve immunization. 25
  • 26. Fever Pain around injection site Muscle aches 26
  • 27. The primary risk associated with vaccines, especially vaccines that utilize live organisms, is that the vaccine itself causes illness. The vaccine may behave as a super antigen and over stimulate the immune system.  Some individual may have an allergic reaction to the vaccines. 27
  • 28. o Approaches for designing a preventive HIV vaccine. o Vaccine against Dengue. o Malaria is mosquito born 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. 28
  • 29. 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. As the vaccines have benefits, they carry some harmful effects too. 29
  • 30. 1. Leo De Leede, Rianne Roukema, Bas Kremer “Advances in Single-shot Vaccine Development” Biopharm International Volume 2009(1). 2. Aungust BJ. International permeation enhancers ,J Pharm Sci.2000;89::429442.doi:10.1002/(SICI)15206017(200004)89:4< 429::AID-JPS 1>3.0.CO;2-J. 3. Vivek Shrivastava and U.K. Jain “Design of Single Dose Control Release Device for Antigen Delivery based on Poly (Lactic-Co- Glycolic Acid)” International Journal of Pharmaceutical Sciences and Nanotechnology, Volume-3,Oct-Dec 2010. 4. Adam A. Walters, Christos Krastew, Adrian V.S. Hill and Anita Milicic, “Next Generation Vaccines: Single-dose Encapsulated Vaccines for Improved Global Immunization Coverage and Efficacy” Journal of Pharmacy and Pharmacology Nov 9,2014 doi:10.1111/jphp.12367. 30
  • 31. 5. http://www.slideshare.net 6. http://en.m.wikipedia.org 7. http://www.youtube.com 8. http://www.google.com Net sources 31
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