Interpandemic Vaccination Controversy, Challenge, Opportunity

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Pandemic influenza vaccine development strategic planning

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Interpandemic Vaccination Controversy, Challenge, Opportunity

  1. 1. Interpandemic Vaccination Controversy, Challenge, Opportunity Robert W Malone, MD, MS [email_address]
  2. 2. Overview: Interpandemic vaccines, a potential business opportunity? <ul><li>Introduction: Interpandemic vaccination, a metaphor for a new approach to vaccine development. </li></ul><ul><li>Context: Is this the right time for serious consideration of this issue? </li></ul><ul><li>Feasibility: Are Interpandemic vaccines technically possible, would they be useful, and could they be viable as product candidates? </li></ul><ul><li>Strategy: Is “pandemic” influenza the right target, or are there others? </li></ul><ul><li>Conclusion: Possible action items. </li></ul>
  3. 3. Interpandemic vaccination, a metaphor for a new approach to vaccine development. <ul><li>Current metaphor: Vaccine products are designed to provide protection against disease caused by currently circulating pathogens and toxins </li></ul><ul><li>Interpandemic metaphor: Develop, license, and implement vaccine products designed to provide protection from potential threat agents (pathogens, toxins, other antigenic biologically active substances) </li></ul>
  4. 4. Interpandemic vaccination, a metaphor <ul><li>Current vaccine metaphor: </li></ul><ul><ul><li>Protection from disease caused by virus, bacteria, or toxin known to represent a significant current public health threat (typically with a well defined cost-benefit ratio) </li></ul></ul><ul><ul><li>Protection from disease caused by an emerging or predictable threat with known biological properties </li></ul></ul><ul><ul><ul><li>Influenza: WHO defined seasonal influenza strains </li></ul></ul></ul><ul><ul><ul><li>Biodefense: Weaponized versions of natural pathogens </li></ul></ul></ul>
  5. 5. Interpandemic vaccination, a metaphor <ul><li>“ Interpandemic” metaphor: </li></ul><ul><ul><li>Protection from disease caused by a potential but not yet circulating biologically active agent. </li></ul></ul><ul><ul><ul><li>Potential pandemic influenza </li></ul></ul></ul><ul><ul><ul><li>Engineered biowarfare/bioterror threats </li></ul></ul></ul><ul><ul><li>A proactive approach to public health in which “herd immunity” may be used to reduce risk of emerging pathogens. </li></ul></ul><ul><ul><ul><li>Constrain evolutionary options available to existing pathogens </li></ul></ul></ul><ul><ul><ul><li>Anticipate and mitigate risks of engineered threat agents </li></ul></ul></ul><ul><ul><ul><li>Complement “chinks in the armor” of existing innate and adaptive immune system </li></ul></ul></ul><ul><ul><li>Associated with unique regulatory affairs “strategic challenges” </li></ul></ul>
  6. 6. Context: Is this the right time ? <ul><li>Pandemic influenza planning and preparation </li></ul><ul><ul><li>Traditional approach inadequate </li></ul></ul><ul><ul><ul><li>Mismatch between epidemiologic modeling and manufacturing/distribution timelines </li></ul></ul></ul><ul><ul><li>Scientific knowledge has advanced </li></ul></ul><ul><ul><ul><li>Molecular virology studies are successfully identifying specific determinants of influenza A infectivity and pathogenesis </li></ul></ul></ul><ul><ul><li>Market exists </li></ul></ul><ul><ul><ul><li>Multiple governments are purchasing and stockpiling vaccine products in anticipation of a pandemic </li></ul></ul></ul><ul><ul><li>Regulatory pathways for licensure have been (partially?) created </li></ul></ul>
  7. 7. Context: Is this the right time? <ul><li>Biodefense: </li></ul><ul><ul><li>Current focus is on known (existing) threat agents </li></ul></ul><ul><ul><li>Near-future focus will be on potential engineered pathogens </li></ul></ul><ul><ul><li>Forward-looking programs (DoD DTRA/JPO-Bio) are identifying biologic mechanisms and pathways which may be exploited to create threat agents (“chinks in the armor”) </li></ul></ul><ul><ul><li>A variety of funding programs are available to support product development </li></ul></ul><ul><ul><li>Novel regulatory solutions for licensure have been created (“correlates of protection, animal rule”) </li></ul></ul>
  8. 8. Feasibility: Interpandemic vaccines All are required for feasibility
  9. 9. Feasibility: Technical considerations (a “reality test” checklist) <ul><li>Is there a need? </li></ul><ul><li>Is there a market? </li></ul><ul><li>Is there sufficient capital? </li></ul><ul><li>Can we identify appropriate target antigens? </li></ul><ul><li>Can we develop vaccine candidates directed against identified antigens? </li></ul><ul><li>Can we demonstrate pre-clinical POC ? </li></ul><ul><li>Can we perform non-clinical pharm/tox? </li></ul><ul><li>Can we identify correlates of protection? </li></ul><ul><li>Can we assess clinical activity? </li></ul><ul><li>Can we assess clinical safety? </li></ul>All are required for feasibility!
  10. 10. Feasibility: Technical considerations <ul><li>Relevant technologies include: </li></ul><ul><ul><li>Molecular modeling </li></ul></ul><ul><ul><li>Genetic drift analysis/phylogenetic modeling </li></ul></ul><ul><ul><li>“ Synthetic” viruses (reverse genetics, reassortants) </li></ul></ul><ul><ul><li>Nucleic acid vaccination </li></ul></ul><ul><ul><li>Engineered VLP </li></ul></ul><ul><ul><li>Peptide vaccines (T and B epitope) </li></ul></ul><ul><ul><li>Novel protein antigen production (Baculovirus etc.) </li></ul></ul><ul><ul><li>Animal model systems (ferret, mouse, chimeric, adoptive transfer) </li></ul></ul><ul><ul><li>Methods for assessing immunologic correlates (microneuts to tetramers) </li></ul></ul><ul><li>Not all vaccine systems may be appropriate </li></ul>
  11. 11. Feasibility: Would an Interpandemic vaccine be useful? <ul><li>The current influenza vaccine manufacturing model may result in vaccine not being available until after the majority of humans have been infected. (+) </li></ul><ul><li>One explanation for the reduced mortality in older cohorts during 1918 epidemic is the earlier circulation of a related strain. (+) </li></ul><ul><li>It is possible that pre-existing titers against a related (slightly mis-matched) strain may reduce potency of strain-matched vaccine. (-) </li></ul><ul><li>Prior examples of seasonal vaccine strain “mismatch” suggest limited efficacy. (-) </li></ul>
  12. 12. Feasibility: Would an Interpandemic vaccine be commercially viable? <ul><li>Currently in US, influenza vaccine is priced as a commodity </li></ul><ul><li>Various approaches currently being explored to differentiate products (Flumist, tetravalent- 2 A strains/2 B strains, filled syringe) </li></ul><ul><li>Inclusion of pre-pandemic antigens in a multivalent seasonal vaccine could be considered </li></ul><ul><li>US DoD could facilitate </li></ul><ul><ul><li>Has supported influenza vaccine innovation </li></ul></ul><ul><ul><li>Administration to DoD personnel under IND could yield robust safety database supporting licensure </li></ul></ul>
  13. 13. Strategy: Is “pandemic” influenza the right target, or are there others? <ul><li>Pandemic influenza: </li></ul><ul><ul><li>Unique current global consensus supporting planning , countermeasure development and stockpiling. </li></ul></ul><ul><ul><li>Emerging recognition and consensus that current vaccine manufacturing and distribution processes may not be adequate- even if there were sufficient capacity! </li></ul></ul><ul><ul><li>Generally high level of public and professional support for planning and stockpiling (contrast to Smallpox vaccine) </li></ul></ul><ul><li>Biological threat agents </li></ul><ul><ul><li>Support (and funding) within specialized communities, public wariness </li></ul></ul>
  14. 14. Conclusion: Possible action items <ul><li>Is there enthusiasm/support for interpandemic vaccine product within governmental and NGO stakeholders </li></ul><ul><ul><li>HHS/BARDA/OEP </li></ul></ul><ul><ul><li>DoD </li></ul></ul><ul><ul><li>WHO </li></ul></ul><ul><li>Is there a pathway to licensure for an interpandemic vaccine product? </li></ul><ul><ul><li>CBER </li></ul></ul><ul><ul><li>EMEA </li></ul></ul><ul><li>Is there support within influenza thought leaders, and what are the objections (if any)? </li></ul><ul><li>Could existing market opportunities be enhanced by adding a interpandemic product? </li></ul>
  15. 15. Thank you for your interest and attention! Personal contact information: Robert Malone, MD, MS 771 Mitchell Road Jasper, GA 30143 Maryland physician license #DOO55466 Office 770 735 1549 Cell 240 994 3334 Email [email_address] Website www.cieloazure.com

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