Recent Developments In Nanovaccine


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Recent Developments In Nanovaccine

  1. 1. Recent developments in nanovaccine 4-May-10 DEPT OF PHARMACEUTICS I.T BHU Presented by: Anand kumar kushwaha M.Pharm IInd sem 09321EN017 Department of pharmaceutics ,I.T BHU Varanasi-221005 1
  2. 2. INTRODUCTION 4-May-10  A vaccine is a biological preparation that improves immunity to a particular disease. DEPT OF PHARMACEUTICS I.T BHU  A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins.  The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters. 2
  3. 3. WORLD HEALTH ORGANISATION: A REPORT 4-May-10 DEPT OF PHARMACEUTICS I.T BHU "Nearly nine million children under 14 years of age die every year from infectious disease. And at least a third of them could be saved if existing vaccines were more widely used, but the rest only if suitable new vaccines were developed..." 3
  4. 4. TYPES OF VACCINE Vaccine are of three types: 4-May-10  DEPT OF PHARMACEUTICS I.T BHU Killed (Inactivated) vaccines Live Toxoids attenuated Exp: Cholera vaccine Exp: Plague Tetanus(fluid/adsorbed) Exp: Diphtheria(adsorbed) Whopping cough Bacillus-calmette-guerin H.Influenza type b Typhoid-ty21a Poliomyelitis oral 4 live(OPV)
  5. 5. NANOVACCINE Nano is very vast field and it can be applied to any 4-May-10  area,one of such area is vaccine. DEPT OF PHARMACEUTICS I.T BHU  It provide a different routes of administration of vaccine.  Nanovaccine can be designed, manufactured and introduced into the human body to improve health, including cellular repairs at the molecular level.  The nanomaterial is so small that it can easily enter the cell; therefore, nanomaterials can be used in vivo or in vitro for biological applications. 5
  6. 6. DELIVERY OF VACCINE:-FOLLOWING ARE THE DIFFERENT WAY TO DELIVER VACCINE AT NANO LEVEL 4-May-10 1.Nanobead: Inert solid bead Size range 20-200nm. DEPT OF PHARMACEUTICS I.T BHU  When antigens are adsorbed on the surface of bead it has been shown to stimulate CD8 -T cell response.  The size of the bead play a major role in eliciting a combined response of humoral and cell-mediated immunity. 6
  7. 7. CONTD…..  Antigen covalently linked to inert nano-beads with a size of ~50 nm is preferentially taken up by DCs, thus 4-May-10 inducing humoral as well as cell-mediated immune responses (Scheerlinck et al. 2006) DEPT OF PHARMACEUTICS I.T BHU 7 *DC;Dendritic cell
  8. 8. 2.POLYMERIC NANOPARTICLES 4-May-10  Biodegradable, biocompatible polymers have been approved for use in humans. DEPT OF PHARMACEUTICS I.T BHU  Poly(D,L-lactide-co-glycolide) (PLG) and polylactide (PLA). antigen adsorbed entrapped 8
  9. 9. CONTD….  PLG have been extensively used to encapsulate 4-May-10 antigens. DEPT OF PHARMACEUTICS I.T BHU  PLG forms lactic and glycolic acids, After hydrolysis of α-hydroxyl acids, yielding small spherical polymeric particles 1–100 nm in size.  Adsorbed antigen offer improved stability and activity over encapsulated antigen by avoiding exposure to organic solvents used during formulation and acidic pH conditions caused by degradation of the polymer. 9 *PLG: polyglycolide
  10. 10. 3.NANOEMULSION Size of globule(100-400nm) 4-May-10   Nanoemulsion vaccine does not require refrigeration and is stable for 6 months. DEPT OF PHARMACEUTICS I.T BHU  Nanoemulsion is non-toxic, pain free and avoids the risk of spreading needle-borne infections.(Makidon et al. 2008)  Nanoemulsion of hepatitis B antigen, has been reported to be a safe and effective hepatitis B vaccine. 10
  11. 11. 4.VIRAL VECTORED VACCINES  Viruses size vary in diameter from 20 nanometres 4-May-10 (nm; 0.0000008 inch) to 250–400 nm.  The immune system quickly respond to viruses, this DEPT OF PHARMACEUTICS I.T BHU would seem to be an ideal way to deliver an antigen.  It consist of a non-replicating virus that contains some defined genetic material from the pathogen to which immunity is desired. Such vaccines are also commonly referred to as live recombinant vaccines.  Viral vectors are: Adenovirus Canary pox virus Yellow fever viruses 11 Modified vaccinia virus ankara (MVA)
  12. 12. CONTD…  Live recombinant viral vector vaccines are constructed by inserting DNA for the desired immunogen into a live, 4-May-10 infections but non-pathogenic virus that elicits a known immune response in DEPT OF PHARMACEUTICS I.T BHU humans.  The most common viral vector is vaccinia first detailed by Moss in 1987. Based on vaccinia's success, there are now more than 20 different RNA and DNA viruses being tested for their applications as Vaccine 12 vectors..
  13. 13. CONTD… 4-May-10  Advantages of virally-vectored vaccines include their ease of production, a good safety profile, ability to potentiate strong immune responses, DEPT OF PHARMACEUTICS I.T BHU potential for nasal or epicutaneous delivery and mucosal immunization.  A recent phase I clinical trial of an adenovirus- vectored flu vaccine administered intranasally and epicutaneously was found to elicit high serum antibody titers with a good safety profile. 13
  14. 14. ADJUVANTS 4-May-10  These substance used in combination with a specific antigen that produced a more robust immunity than the antigen alone. DEPT OF PHARMACEUTICS I.T BHU  It improve the immune response to vaccine antigen by different way: Increasing immunogenicity of weak antigen. Enhancing the speed and duration of the immune response. Modulating antibody avidity,specifity,isotope or subclass distribution. 14
  15. 15. EXAMPLES 4-May-10 MF59 Monophosphoryl lipid A DEPT OF PHARMACEUTICS I.T BHU Montanide™ Calcium phosphate nanoparticles. Immunostimulating complexes Cholesterol-bearing hydrophobized pullulan nanoparticles (CHP) 15
  16. 16. MF59 4-May-10  MF59 is the only nano-sized vaccine adjuvant approved for human use. DEPT OF PHARMACEUTICS I.T BHU  MF59 is an oil-in-water emulsion ( ≤ 250 nm droplets)  Its showed a 34-fold increase in antibody titers when immunized with glycoprotein D of herpes simplex virus (HSV) in guinea pigs.  The mechanism of adjuvanticity of MF59 is believed to be through direct stimulation of cytokine production (J.K. Simon 16
  17. 17. MONOPHOSPHORYL LIPID A 4-May-10  Monophosphoryl lipid A (MPL®) is an immunostimulating TLR-4 receptor agonist composed of detoxified lipopolysaccharide (LPS) DEPT OF PHARMACEUTICS I.T BHU from Salmonella minnesota R595.  It is a versatile vaccine adjuvant that may be included in aqueous formulations or in an oil-in- water emulsion for a more dynamic response. 17
  18. 18. MONTANIDE™ 4-May-10  There are several different types of Montanide™, DEPT OF PHARMACEUTICS I.T BHU including ISA 50V, 51, 206 and 720.  ISA 50V, 51 and 720 are water-in-oil emulsions while ISA 206 is a water-in-oil-in-water emulsion.  ISA 206 and 50V only used in veterinary vaccine formulations.  ISA 51 & ISA 720 are under investigation for use in humans. 18
  19. 19. CONTD….  Emulsions of Montanide™ ISA 51 and 720 are 4-May-10 composed of a metabolizable squalene-based oil with a mannide monooleate emulsifier. DEPT OF PHARMACEUTICS I.T BHU  The immune enhancement produced by the Montanide™ emulsions is believed to be due to the formation of a depot at the site of injection. (A.P. Miles, 2005)  The emulsion vaccines against malaria, HIV and various cancer have been in phase I and/or II clinical trials.  A phase I trial of a trivalent malaria vaccine containing ISA 720 induced both humoral and 19 cellular immune responses( A. Saul,1999)
  20. 20. CALCIUM PHOSPHATE NANOPARTICLES 4-May-10  Calcium phosphate nanoparticles are less than 1000nm in diameter. DEPT OF PHARMACEUTICS I.T BHU  Nanoparticles can be generated by combining (while stirring) calcium chloride, sodium phosphate and sodium citrate.  It produces longer duration of response as compare to Al salt.  Phase I study showed that CaP is safe and non-toxic when administered subcutaneously.  Vaccines utilizing CaP in preclinical studies include anthrax, HBV, flu (H5N1 avian and seasonal) and HSV-2. 20 *HBV: Hepatitis B virus *HSV: Herpes simplex virus
  21. 21. IMMUNOSTIMULATING COMPLEXES 4-May-10  Another vaccine delivery vehicle with potent adjuvant activity. DEPT OF PHARMACEUTICS I.T BHU  Produced by combining a protein antigen, cholesterol, phospholipid and the saponin adjuvant Quil A.  These are ~40 nm cage-like particles.  The matrix that is formed traps the protein antigens. 21 Quill A: Quillaia saponaria (molina tree)
  22. 22. CONTD… COMPARISON OF ISCOM WITH CLASSICAL INFLUENZA VACCINE. 4-May-10  ISCOM induce stronger immune response in comparison to classical influenza vaccine. DEPT OF PHARMACEUTICS I.T BHU  ISCOM based flu vaccine showed that virus- specific CTL memory was achieved in 50–60% of the patients while in case of classical influenza it is only 5%.  Intranasally administration of ISCOM flu vaccine showed strong mucosal (IgG and IgA) responses as well as systemic and CTL responses.  Oral vaccine of ISCOM also effective but requires high and frequent dosing. 22
  23. 23. CHOLESTEROL-BEARING HYDROPHOBIZED PULLULAN NANOPARTICLES (CHP) 4-May-10  Pullulan is the most popular polysaccharide to which cholesterol can be Conjugated. It render the molecules amphiphilic. DEPT OF PHARMACEUTICS I.T BHU  Such molecules have been shown to self assemble with and without proteins into 30–40 nm colloidally stable nanoparticles.  Its size and density can be modified by altering the degree of substitution of cholesterol groups on the polysaccharide. A preclinical study in mice showed that immunization with a complex of the HER2 oncoprotein and CHP induced both humoral and CD8 responses. 23 *HER: Human epidermal growth factor receptor 2
  24. 24. ADVANTAGES OF NANOVACCINE 4-May-10  Nanovaccine have potential to deliver safe and more effective vaccine. DEPT OF PHARMACEUTICS I.T BHU  Nanobead covalently coupled with antigen offer distinct advantages – a low dose of antigen is required, efficient processing by antigen-presenting cells and stability during storage.  Encapsulated nanoparticles easily deliver antigen, protects the antigen from degradation and is found to be effective with a single dose due to slow release of the antigen. 24
  25. 25. CONTD…  Many of the nanovaccines are non-invasive, delivered 4-May-10 by the oral or nasal route, diffusion patches or microneedle arrays, thus allowing pain-free delivery with minimal damage. This is an advantage over DEPT OF PHARMACEUTICS I.T BHU conventional vaccines,which are usually multi- injection, multi-dose delivery systems.  The nanoemulsion preparation of hepatitis B antigen found to be tolerable and effective and does not require refrigeration and it is effective for a month at 25ºc and for 6 week at 40ºc,therefore it facilitate its final distribution in small areas/villages of developing countries. 25
  26. 26. DISADVANTAGES OF NANOVACCINE 4-May-10  Cost of production.  Nanomaterials can change size, shape but not DEPT OF PHARMACEUTICS I.T BHU composition, which may change their toxicity.  Small nanoparticles are cleared quickly from the body, large counterparts may accumulate in vital organs causing toxic problems.  Reproducibility of formulation during manufacturing is one of the major hurdles in the use of nanoparticles as vaccines. 26
  27. 27. FUTURE PROSPECTS 4-May-10  Carbon nanotubes may be used to deliver vaccine.  Peptide–nano-bead based vaccine approach may be DEPT OF PHARMACEUTICS I.T BHU beneficial, especially for highly variable pathogens such as FMDV(foot and mouth disease virus).  Nanoemulsion may deliver smallpox, influenza, anthrax and HIV vaccines.  Nanoemulsion against GP 120, one of the major binding proteins, may induce mucosal and cellular immunity, and neutralize antibody to various isolates of HIV.  Adenovirus may deliver vaccine for Alzheimer's 27 disease ,influenza ,tetanus and HIV based vaccine.
  28. 28. REFERENCES 4-May-10 1 Tarala D nandedkar, Nanovaccines: recent developments in vaccination, J. Biosci. 34 000–000 2009. DEPT OF PHARMACEUTICS I.T BHU 2 J. Peek Laura, Nanotechnology in vaccine delivery, Advanced Drug Delivery Reviews 60 (2008) 915–928, 3 J. Bharali Dhruba, Novel nanoparticles for the delivery of recombinant hepatitis B vaccine, Nanomedicine: Nanotechnology, Biology, and Medicine 4 (2008) 311–317. 4 Cui Zhengrong, The effect of co-administration of adjuvants with a nanoparticle-based genetic vaccine delivery system on the resulting immune responses, European Journal of Pharmaceutics and 28 Biopharmaceutics 55 (2003).
  29. 29. 4-May-10 DEPT OF PHARMACEUTICS I.T BHU 29