concept of Vaccine introduction,antigen uptake,single shot vaccine
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A seminar on Vaccine,Uptake of antigen, Single shot vaccine 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
History of vaccine 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
History 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
History 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
What are vaccines ….??? 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
Types of vaccines Vaccines are dead or inactivated organisms or purified product derived from them. The different types of vaccines are ; Traditional vaccines Innovative vaccines 7
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
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Stages of exogenous antigen processing 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
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FFFig Fig- Exogenous antigen processing 15
Endogenous antigen processing 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
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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
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 . 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
Formulation and Manufacturing of Single-Shot Vaccines 22
Delayed antigen r elease 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 c onsideration 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
Adverse effect Fever Pain around injection site Muscle aches 26
Risk associated The primary risk associated with vaccines, especially vaccines that utilize live organisms, is that the vaccine itself causes illness. T he vaccine may behave as a super antigen and over stimulate the immune system. S ome individual may have an allergic reaction to the vaccines. 27
Recent trends Approaches for designing a preventive HIV vaccine. Vaccine against Dengue. 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
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. As the vaccines have benefits, they carry some harmful effects too. 29
References Leo De Leede, Rianne Roukema, Bas Kremer “Advances in Single-shot V accine Development” Biopharm International Volume 2009(1). 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. 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. Adam A. W alters, 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