1 / 25

Pandemic vaccines: development status

Pandemic vaccines: development status. Martine Denis Beijing Jan 29, 2007. Pandemic vaccine development: an usual framework. Typical diseases justifying vaccine development * Well defined pathogen * Established burden of disease * Clear needs in terms of vaccine indication and

vincent-hernandez
Download Presentation

Pandemic vaccines: development status

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. Pandemic vaccines: development status Martine Denis Beijing Jan 29, 2007

  2. Pandemic vaccine development: an usual framework Typical diseases justifying vaccine development * Well defined pathogen * Established burden of disease * Clear needs in terms of vaccine indication and logistics of administration

  3. Pandemic vaccine development: an usual framework Typical diseases justifying vaccine development * Well defined pathogen * Established burden of disease * Clear needs in terms of vaccine indication and logistics of administration Pandemic influenza * Unknown / unpredictable influenza virus * Disease inexistent as of today, but could be severe and affect all pop. worldwide  Political / economical considerations * Variable / poorly defined vaccination strategies (e.g. stockpiling…) * Several lessons from the past (e.g. Spanish flu, swine flu…)

  4. Epidemiology data: Global spread of H5N1 infection in birds and increasing number of human cases H5N1 virus mutating in a way that may make it more infectious to humans Only 2 amino acid changes in the receptor-binding pocket of H5 would yield a virus that efficiently recognizes receptors on human cells  The next pandemic may be imminent The H5N1 threat Mills et al. PLOS Medicine 2006;3(6):e135 Garten et al. Atlanta: International Conference on Emerging Infectious Diseases; 2006 Harvey et al. J.Virol. 2004;78(1):502-7

  5. First immunogenicity data: Unadjuvanted split inactivated H5N1 vaccine poorly immunogenic in humans H5 dose (µg) % subjects w. titer  1 :40 90 54 45 43 15 22 7.5 9 The H5N1 threat NEJM 2006; 354:1343-51

  6. Epidemiology data: The next pandemic may be imminent First immunogenicity data: Unadjuvanted H5N1 vaccine poorly immunogenic DEVELOPMENT OF NEW PANDEMIC VACCINES = CRITICAL H5N1 used as prototype pandemic strain The H5N1 threat

  7. A pandemic vaccine: Should be producible in volumes matching needs Should be safe Should be approved by regulatory authorities in reasonable timeframe Pandemic vaccine development objectives

  8. Pandemic vaccine technologicals options Egg-based manufacturing Cell-based manufacturing Inactivated vaccines DNA vaccines; recombinant proteins Live vaccines

  9. Pandemic vaccines: clinical development status Phase II Filed Phase I Phase III Berna Viro- somes Med Immune LAV Japan Whole / Al GSK Whole/ Al SP Split / Al CSL Whole/ Al Baxter Whole/ Al GSK Split/ AS Berna Whole/ Al Merck M2 Novartis Surf Ag/ MF59 CSL Split / Al Source: IFPMA R&D table Oct 06

  10. Regulatory file submission = key step in vaccine development Vaccine composition defined Vaccine presentation defined Preclinical and clinical data available to support vaccine safety and immunogenicity Manufacturing process defined Manufacturing facilities available Pandemic vaccines and regulatory file submissions

  11. Immunogenicity of whole / Alum H5N1 vaccine Adults aged 18-60 years, post dose 2 CHMP criteria Low doses of H5 induce low levels of antibodies Jiangtao Lin, et al. www.thelancet.com DOI:10.1016/S0140-6736(06)69340-9

  12. Immunogenicity of GSK whole / Alum H5N1 vaccine Adults aged 18-60 years, post dose 2 15µg H5 required to pass all 3 CHMP registration criteria Saenger IVW Vienna Oct 2006

  13. Immunogenicity of split / Alum H5N1 vaccine Adults aged 18-40 years, post dose 2 Alum provides modest enhancement of the antibody response Bresson J-L, et al. www.thelancet.com DOI:10.1016/S0140-6736(06)68656-X

  14. Immunogenicity of GSK low dose AS adjuvanted H5N1 vaccine Upon formulation with AS, 3.8µg H5 enough to pass all 3 CHMP registration criteria CHMP criteria 70 Borkowski IVW Vienna Oct 2006 106750/NCT:00309634

  15. Low dose H5N1 vaccine feasible upon combination with potent adjuvant Seasonal: 45µg 12-fold capacity increase Pandemic: 3.8µg Suitable pandemic vaccine composition identified

  16. Pandemic vaccine: available too late? UK model: Epidemic peaks in ~50 days from the first case (~90-120 days after initial outbreak) (Ferguson et al. Nature 2006, April 26)

  17. Pandemic vaccine: available too late? UK model: Epidemic peaks in ~50 days from the first case (~90-120 days after initial outbreak) (Ferguson et al. Nature 2006, April 26) Manufaturing the first lot of vaccine takes approximately 3 months

  18. A stockpile offers potential for earlier protection A pre-pandemic vaccine: Should be producible in volumes matching needs Should be safe Should be approved by regulatory authorities in reasonable timeframe Shouldinduce immunity against drift influenza strains Shouldhave a multi-year shelf life Stockpiling with a pre-pandemic vaccine: a proactive approach

  19. Pre-pandemic vaccine: technological options to induce immune cross-reactivity AS ADJUVANTS MF59 Whole virus Alternative antigens M2 proteins

  20. GSK AS adjuvanted vaccine cross-protects ferrets in heterologous H3N2 challenge IN challenge (Wyoming) Day 2 post challenge P <0.001 Vaccination (Panama) The AS adjuvant is key to induction of cross-protection in the ferret model Baras IVW Vienna Oct 2006

  21. Immune cross-reactivity with whole / Alum H5N1 vaccine Vaccine strain: Vietnam/1203/04 (clade 1) Testing: microneutralization against Indonesia/05/05 (clade 2) N.B. preliminary data Fair levels of cross-neutralization detected between strains as distant as Vietnam and Indonesia Baxter Vaccines IVW Vienna Oct 2006

  22. Only planning for manufacturing during pandemic Protection 1st dose 2nd dose 3-4 weeks Cross Protection “3rd”dose Direct Protection Manufacturing of prepandemic vaccine 1st dose 2nd dose 3-4 weeks months or years Pandemic Preparedness Options World-wide H5N1 Pandemic Phase 3 Phase 4 Phase 5 Phase 6 : PANDEMIC Time Manufacturing of prepandemic vaccine Protection 1st dose 2nd dose 6 months Pre-Pandemic Vaccine Pandemic Vacc.

  23. A vaccine for pregnant women? Infants? Immunocompromised?...etc Duration of immunity to drift strains? Breadth of immunity to drift strains? How to combine pre-pandemic and pandemic vaccines? Number of doses? Interval between doses?...etc ??? Pandemic / pre-pandemic vaccine development: a long journey

  24. Significant progress over the past months: H5N1 pandemic and pre-pandemic vaccine feasibility established Several regulatory files submitted (pandemic and pre-pandemic); one positive opinion granted by EMEA Partnership between manufacturers and health authorities is key CONCLUSIONS

More Related