1 / 17

The more Effective FLU VACCINE PROBLEM

Explore the perpetual challenge of responding to influenza, vaccine limitations, the need for more effective vaccines, and the landscape of innovative developments in influenza vaccine research.

maryhunter
Download Presentation

The more Effective FLU VACCINE PROBLEM

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. 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.

More Related