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The more Effective FLU VACCINE PROBLEM

The more Effective FLU VACCINE PROBLEM. WHO Meeting August 23, 2016. Source: Abbas, Abul K, Andrew H. Lichtman , and Shiv Pillai. Cellular and Molecular Immunology . Philadelphia: Saunders/Elsevier, 2010. Print. Resilient People. Healthy Communities. A Nation Prepared.

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The more Effective FLU VACCINE PROBLEM

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  1. The more Effective FLU VACCINE PROBLEM WHO Meeting August 23, 2016 Source: Abbas, Abul K, Andrew H. Lichtman, and Shiv Pillai. Cellular and Molecular Immunology. Philadelphia: Saunders/Elsevier, 2010. Print. Resilient People. Healthy Communities. A Nation Prepared.

  2. Perpetual challenge of responding to influenza 1918 ‘Spanish’Pandemic Allcountries affected 20%-40%infectedworldwide 50Mdeathsworldwide 675,000deathsin US 2009-H1N1Pandemic 74 countriesaffected 60.8M infectedin U.S. 123,000-203,000deathsworldwide 12,469 deathsinUS 274,304 hospitalizations in US SeasonalInfluenzaEpidemic inUS 5%-20%of population infected year 3,000-49,000 deaths everyyear >200,000hospitalizations $87.1B economicburden everyyear $10.4Bmedicalcosts everyyear

  3. BARDA is achieving national pandemic vaccine goals More, faster to More, faster & better!

  4. Limitations of current influenza vaccines • Vulnerable to antigenic drift and shift • Antibodies target highly variable regions of HA and NA • Single site mutations can impact immunogenicity • Provide minimal cross-protection within subtypes or against other subtypes of influenza • Short duration of immunity, particularly in at-risk populations (e.g., pediatric, geriatric) • Requires viral isolate for production • Predominantly produced in chicken eggs • Avian influenza strains will likely require adjuvant • Vaccine efficacy is modest There is need for more effective influenza vaccines

  5. Innate and adaptive immunity Source: Abbas, Abul K, Andrew H. Lichtman, and Shiv Pillai. Cellular and Molecular Immunology. Philadelphia: Saunders/Elsevier, 2010. Print. Most vaccines in use today work by inducing humoral immunity

  6. Optimizing Humoral Immunity Adjuvants By permission K. Erlandson Cross-reactive stalk-based epitopes Antigenically advanced vaccines Structure-based modification of HA specificity By permission D. Smith, R. Fouchier, Y. Kawaoka Rationally designed heterologous prime boost

  7. Role of CMI • No correlation between pre-existing influenza- • specific total-cytokine- • secreting T-cells to live virus and rate of infection • The frequency of pre-existing cross-reactive T cells is inversely associated with illness severity Not everyone is primed to respond with a CMI response Higher frequency of baseline T cells in virus non-shedder

  8. Severe H7N9 disease immune protection model

  9. Conservation of T-cell epitopes Certain influenza virus T-cell epitopes are shared more than others

  10. Population Impacts of Improved Vaccine Could we consistently reduce these P&I mortality spikes? Could we reduce Peds deaths? The efficacy of influenza vaccine can be assessed at both the individual and population level

  11. Mucosal Immunity Source: Abbas, Abul K, Andrew H. Lichtman, and Shiv Pillai. Cellular and Molecular Immunology. Philadelphia: Saunders/Elsevier, 2010. Print. The potential of mucosal immunization to impact CMI is not yet clear. Are adjuvants needed? Source: Markus A Rose, Stefan Zielen & Ulrich Baumann (2012) Mucosal immunity and nasal influenza vaccination, Expert Review of Vaccines, 11:5, 595-607, DOI: 10.1586/erv.12.31

  12. Innate immunity? Source: Abbas, Abul K, Andrew H. Lichtman, and Shiv Pillai. Cellular and Molecular Immunology. Philadelphia: Saunders/Elsevier, 2010. Print. Can/should innate immunity be primed for influenza prophylaxis?

  13. More Effective Influenza Vaccines: Bringing it all together • MF59, AS03, • poly IC, Resiquimod, • other TRL agonists • Innate immunostimulators? • IIV, attenuated vectors, recombinant – VLPs and nanoparticles, • nucleic acid • Epitope content, structure • Humoral, CMI, • mucosal, innate • Oral, intranasal, injection • HtPB • Boost regimen

  14. More effective influenza vaccine: Target Product Profile

  15. Landscape of more effectiveinfluenza vaccine candidates There is a need for specific and convincing immunological data Data is lacking ? Presence of desirable immune response

  16. More effective influenza vaccine development pipeline at BARDA

  17. The more Effective FLU VACCINE PROBLEM….….Next STEPS Resilient People. Healthy Communities. A Nation Prepared.

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