1 / 16

I m m u n o l o g I c A d j u v a n t s

Freddy Choy Joyce Lau. I m m u n o l o g I c A d j u v a n t s. Agenda. What are Adjuvants History of Adjuvants Reason for Adjuvants Factors Affecting Adjuvant Efficacy “Ideal Adjuvant”. Common Issues of Adjuvants Types of Adjuvants Adjuvant in Research Vaxjo Regulatory Hurdles

tasha
Download Presentation

I m m u n o l o g I c A d j u v a n t s

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Freddy Choy Joyce Lau I m m u n o l o g I c A d j u v a n t s

  2. Agenda • What are Adjuvants • History of Adjuvants • Reason for Adjuvants • Factors Affecting Adjuvant Efficacy • “Ideal Adjuvant” • Common Issues of Adjuvants • Types of Adjuvants • Adjuvant in Research • Vaxjo • Regulatory Hurdles • Future Outlook

  3. What are Adjuvants? • Adjuvare [Latin] - to help, to enhance • Any product (or association of components) that increases or modulates the humoral or cellular immune response against an antigen • “Universal adjuvant” non existent

  4. History of Adjuvants • 1925: Observed that the highest antibody titers when local inflammation was induced by concomitant injection of other substances – tapioca, aluminum salts, lanolin etc. • 1926: Introduced use of aluminum hydroxide as adjuvant in diphtheria toxoid

  5. Reasons for Adjuvants • To enhance the immunogenicity and potency of highly purified or recombinant antigens • Reduce the amount of antigen required; and subsequent immunizations • To improve the efficacy of vaccines in newborns, the elderly or immuno-compromised persons • As antigen delivery systems for the uptake of antigens by the mucosa

  6. Factors Affecting Adjuvant Efficacy • Limited knowledge of disease pathogenesis • Knowledge of MOA • Target population • Genetic variation • Host immune status • Formulation of the vaccine + adjuvant • Dose, combination, etc.

  7. “Ideal Adjuvant” • Safe and free from immediate + long-term side effects • Biodegradable / easily excreted after adjuvant has elicited its effects • Exhibit protective / therapeutic immune response when combined with antigen • Chemically and biologically defined • Efficacy of vaccine achieved with fewer doses / lower concentration of antigen • Shelf stable • Affordable

  8. Common Issues of Adjuvants • Little known about MOA • Frequently induce toxicity • Strong local stimulation • Carcinogenesis • Complicated preparations

  9. Types of Adjuvants • Mineral Salts:Aluminum salts • Standard adjuvant approved for human use • Poor at inducing cellular immune response • Potential for aluminium intoxication • Emulsions:two immiscible liquids stabilized with surfactants/emulsifiers • Allows slow release of antigen • Highly toxic

  10. Types of Adjuvants • Microorganism-derived: Bacterial or fungal substances • i.e. bacterial cell wall peptidoglycan or LPS • Stimulates humoral & cellular responses • Particulates: microscopic particles • Virosomes – induce potent immune response • Liposomes – potency depends on # of lipid layers, electric charge, composition & preparation method • Nano-beads – induce substantial cell mediated response & moderate humoral response

  11. Adjuvant in Research • Phytol: natural, dietary diterpene alcohol • PHIS-01: hydrogenated derivative • 2 recent studies in mice; similar findings • Low pro-inflammatory effects • Small amounts of phytol + PHIS-01 required to stimulate immune responses • PHIS-01 appears to be more useful than phytol

  12. Vaxjo • Central web-based vaccine adjuvant database and analysis resource • Compliments VIOLIN • Published in the Journal of Biomedicine and Biotechnology in 2011 • Comprehensive to include a large variety of infectious diseases, and diseases including cancer and allergies • Challenges and obstacles • http://www.violinet.org/vaxjo/

  13. Regulatory Hurdles • Preclinical studies on adjuvant • Same route of administration • Dose & frequency similar to proposed • Toxicology studies on antigen-adjuvant formulation • Large population size required for testing

  14. Future Outlook • Approval for additional human adjuvants • Safer alternatives • Longer lasting and stronger immunogenicity • Define reliable animal models for adjuvant studies • Define study protocols for safe and pivotal observations • Determine standards to test lots of adjuvants

  15. Thank you!

  16. Works Cited • Petrovsky N., Aguilar J.C. Vaccine adjuvants: current state and future trends. Immunol Cell Biol 2004;82(5):488–96. • Vogel F.R. Adjuvants in perspective. In: Brown F, Haaheim LR, editors. Modulation of the immune response to vaccine antigens. Dev. Biol. Stand. vol 92. Basel: Karger; 1998. p. 241–8. • Lima K.M., Aparecida dos Santos S., Rodrigues J.M. Jr., Silva C.L. Vaccine adjuvant: it makes the difference. Vaccine 2004; 22:2374–2379. • Ramon G. Sur l’augmentationanormale de l’antitoxine chez les chevauxproducteurs de serum antidiphterique. Bull SocCentr Med Vet 1925;101:227–34. • Ramon G. Procedes pour accro¨ıtre la production des antitoxins. Ann Inst Pasteur 1926;40:1–10. • Allison A.C., Byars N.E. Immunological adjuvants: desirable properties and side-effects. Mol Immunol 1991;28:279–84. • Aguilar J.C., Rodriguez E.G. Vaccine adjuvants revisited. Vaccine 2007; 25:3752–3762 • Freund J. The mode of action immunological adjuvants. AdvTuberc Res 1956;7:50–5. • Cox J. C., Coulter A. R. Adjuvants – a classification and review of their modes of action. Vaccine 1997;15:248-256. • Lim, S-Y., Meyer, M., Kjonaas, R.A., Ghosh, S.K. Phytol-based novel adjuvants in vaccine formulation: 1. Assessment of safety and efficacy during stimulation of humoral and cell-mediated immune responses. Journal of Immune Based Therapies and Vaccines 2006; 4:6. • Aachoui, Y., Ghosh, S.K., Immune enchancement by novel vaccine adjuvants in autoimmune-prone NZB/W F1 mice: relative efficacy and safety. BMC Imunology 2011; 12:61. • Walker, J.M. (2000). Vaccine Adjuvants: Preparation Methods and Research Protocols. D. T. O’Hagan (Ed.). Emeryville, CA: Humana Press. • Lima, K.M., dos Santos, S.A., Rodrigues, Jr., J.M., Silva, C.L., Vaccine adjuvant: it makes the difference. Vaccine 2004; 22:2374-2379. • Bagherwal, P., Dwivedi, S.K. A Review: Adjuvants Designed for Vaccine. International Journal of Pharmaceutical & Research Sciences 2012; 1(2):113-126. • Brennan F. R., Dougan G. Non-clinical safety evaluation of novel vaccines and adjuvants: new products, new strategies. Vaccines 2005;23:3210-3222. • The European Agency for the Evaluation of Medicinal Products. Guideline on Adjuvants in Vaccines v5 Consultation (25 March 2004). • Couch RB. Nasal vaccination, Escherichia coli enterotoxin, and Bell’s palsy. N Engl J Med 2004;350:860–1. • Murphy TV, Gargiullo PM, Massoudi MS, Nelson DB, Jumaan AO, Okoro CA, et al. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med 2001;344:564–72.

More Related