Single shot vaccines Naveen Balaji
- 1. SINGLE SHOT VACCINES Under guidance of: Dr. K. Manjunath,M.Pharm,Ph.D., Professor & HOD Department of Pharmaceutics Sree Siddaganga college of pharmacy Tumakur. Presented by: NAVEEN BALAJI 1st M.Pharm Department of Pharmaceutics Sree Siddaganga college of pharmacy Tumakur. 1
- 2. CONTENTS Introduction. Concept. Formulation and Manufacturing of single shot vaccine. Factors affecting Antigen release. Adverse effects. Advantages. Disadvantages & Risks. Conclusion. 2
- 3. INTRODUCTION • Single shot vaccines are given for preventing 4 to 6 diseases with only one injection. • To provide effective patient protection, many traditional vaccines requires 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. 3
- 4. CONCEPT • The single-shot vaccine is a combination product of a prime component antigen with an appropriate adjuvant and a microsphere component. • In order to increase the therapeutic efficiency of such vaccines, adjuvants are used. • microsphere component that encapsulates antigen and provides the booster immunizations by delayed release of the antigen. 4
- 5. • The microsphere component uses OctoVAX microsphere technology, which is based on cross-linked modified dextran polymers. • Dextrans are ideal polymers to form biocompatible hydrogels, Two major advantages of dextran microspheres as protein delivery systems, that the particles are prepared in the absence of organic solvents, and that degradation of the microspheres does not result in a pH drop. • Several different dextrans have been developed for hydrogel formation. One of these dextran-based polymers is derivatized with hydroxy-ethyl methacrylate (Dex-HEMA). • Which introduces hydrolytically sensitive carbonate ester groups that ensure biodegradation under physiological conditions. 5
- 6. FORMULATION AND MANUFACTURING OF SINGLE SHOT VACCINE :- • VACCINE ADJUVANTS :- • Adjuvants are the substances added to vaccines to help them work better. Adding an adjuvant triggers the immune system to become more sensitive to the vaccine. • NEED FOR ADJUVANTS :- • To increase the therapeutic efficiency. • They form depot of antigen at the site of inoculation with slow release of antigens. • It can improves the performance of vaccines by targeting the antigen to APC . 6
- 7. Types of Adjuvants :- • Gel types eg. :- aluminum hydroxide, calcium phosphate. • Oil emulsion and emulsifier Particulate based type eg :- liposomes , biodegradable microspheres. 7
- 8. BIODEGRADABLE POLYMERS :- • Biodegradable polymers are defined as polymers comprised of monomers linked to one another through functional groups and have unstable links in the backbone. • Broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways 8
- 9. TYPES OF BIODEGRADABLE POLYMERS :- • There are two types of biodegradable polymers. They are :- 1) Natural biodegradable polymers :- eg : Albumin, Collagen, Gelatin etc.,. 2) Synthetic biodegradable polymers :- eg : Aliphatic poly(esters), Pseudo poly aminoacid , etc., 9
- 10. BIODEGRADABLE POLYMERS AS ADJUVANTS :- • Biodegradable polymers such as poly( lactide - co-glycolic acids) is most commonly used for vaccine delivery. • This polymer is mainly required for controlled release of the drug from polymer matrix. • Targeting to appropriate cell types to generate optimum response. • Development of formulation that can be used as non- invasive. 10
- 11. Important factors in the manufacture of a microsphere based vaccine are high encapsulation efficiency and a consistent particle-production process. Several formulation parameters play an important role in obtaining a robust process. 11
- 12. • Dex-HEMA is very much 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. 12
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- 14. • To ensure consistently high encapsulation efficiencies, the protein to be encapsulated is added to the dex-HEMA solution before adding the PEG solution. • Subsequently, microspheres are obtained by polymerizing the HEMA groups using potassium persulfate (KPS) as initiator and N,N,N',N'-tetramethylethylenediamine (TEMED) as the catalyst 14
- 15. • Several factors are critical parameters for the formulation of consistent microspheres. First, the size distribution of the microspheres can be controlled by the shear force applied during the emulsification step in the bioreactor vessel. 15
- 16. Bioreactor used during scale-up of the production process 16
- 17. Controlling Particle Size During Process Scale-up • The dextran microsphere preparation method is described by Stenekes was initially performed on a 5-g scale (containing 120 mg of microspheres), and used vortexing to emulsify the dex-HEMA phase in the continuous PEG phase. 17
- 18. • Microscopic pictures of microspheres produced at a high stirring speed of 700 rpm 18
- 19. • A direct correlation was observed between stirring speed and mean particle diameter of the microspheres, thus confirming that the particle size of the dextran emulsion is dependent on the energy input during emulsification. • It is important to note that, despite the larger mean diameter of microspheres prepared at the 500-g scale, more than 90% of the resulting particles had a size below 90 μm, a size suitable for subcutaneous injection. 19
- 20. 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. 20
- 21. Factor affecting antigen release :- • 1. Polymer nature • 2. Crystallinity • 3. Method of preparation • 4. Molecular weight of drug • 5. Carrier size and morphology 21
- 22. Adverse effects :- • Fever • Pain around injection site • Muscle aches 22
- 23. ADVANTAGES • Economic. • With one Injection 4 to 6 Infections can be prevented. • Patient compliance is Improved because, they would replace the need for a prime boost regimen, consequently eliminating the repeated visits to the doctor for mother and their children. 23
- 24. DISADVANTAGES & RISKS :- • The primary risk associated with vaccines, especially vaccines that utilize live organisms, so that the vaccine itself causes illness. • The vaccine may behave as a super antigen and over stimulate the immune system. • Some are not as effective as Multi-dose vaccines, because infection can occur due to micro organisms. 24
- 25. Conclusions • The development of a single-shot vaccine technology could contribute to a significant increase in vaccination coverage worldwide by improving patient compliance and lowering administration costs. • To achieve this innovation, single-shot vaccines must be rationally designed. 25
- 26. •To facilitate this, complex factors in the development and manufacturing process that have a significant influence on the efficacy of the immune response must be controlled precisely during the development and manufacturing phase. 26
- 27. REFERENCES :- • www.Google.com. • Leo De Leede, Rianne Roukema, Bas Kremer “Advances in Single- Shot Vaccine Development” Biopharm International Volume 2009. • Vivek Shrivatsava & U.K.Jain “Design of Single Dose Control Relese Device for Antigen Delivery based on Poly(Lactic-co-Glycolic acid)” • International journal of Pharmaceutical Sciences & Nno technology, volume 3, 2010. • Adam.A.Walters, Christos Krastew, Adrian V.S.Hill & Anita Milicic, “Next Generation Vaccines; Single Dose Encapsulated vaccines for Improved Global Immunization Coverage & Efficacy” Journey for Pharmacy And Pharmacology Nov 9,2014. 27
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