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The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
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The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines

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  • The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
  • My objective...This will be done in the context of the PCIRN RT-03 StudySubjects were given the Canadian pandemic H1N1 influenza vaccine...And essentially, our hypothesis is that...
  • STUDY RESULTSEpub Dec 2010The RT-03 was completed between November 2009 and January 2010(Pediatric) study showed that one pediatric dose of adjuvanted pH1N1 vaccine elicited potentially protective titers (≥ 40) in 80% of seronegative children while a second dose raised this to 100% and increased GMT by 10-fold.  Naturally primed children had strong responses; such high titers may afford greater or longer-lasting protection.
  • Geometric mean with 95% confidence intervalof HAI, MN, Avidity ELISAs
  • Transcript

    • 1. The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines<br />Karen K. Yam, Ph.D.<br />Post-doctoral Fellow (Brian Ward Lab)<br />PCIRN Annual Meeting<br />Wednesday April 20th, 2011<br />
    • 2. Objectives<br />Understand the influence of adjuvants on long-term humoral responses to influenza following vaccination<br />PCIRN RT-03 Study<br />Canadian pH1N1 influenza vaccine<br />ASO3 adjuvant<br />25% of the antigen dose of regular vaccine<br />Hypothesis<br />Low dose of antigen in adjuvanted vaccine may enhance the short-term response at the expense of the long-term immunity<br />
    • 3. PCIRN RT-03 Study<br />167 pediatric subjects (6-35 months)<br />Arepanrix vaccine<br />ASO3-adjuvanted pH1N1(2009)<br />Visit 1<br />Visit 2<br />Visit 3<br />Day:<br />0<br />21<br />42<br />80%<br />seroprotected<br />100%<br />seroprotected<br />
    • 4. Methods:Sample selection<br />RT-03 serum samples in the PCIRN archive<br />Selected:<br />All 3 timepoints available<br />V1, V2, V3<br />73 subjects selected<br />
    • 5. Methods:Serum Analysis<br />Hemagglutination Inhibition (HAI) assay<br />Titer of flu-specific Abs<br />National Microbiology Laboratory<br />Micro-neutralization (MN) assay<br />Titer of functional Abs that can neutralize viral entry<br />Avidity Index ELISA<br />Measure of the binding strength of flu-specific Ab<br />Read-out for the development of humoralimmresp<br />
    • 6. Affinity/Avidity Maturation<br />Humoral immune response<br />B<br />ag<br />B cell<br />Antibodies<br />
    • 7. Affinity/Avidity Maturation<br />B<br />B<br />B<br />B<br />ag<br />ag<br />ag<br />ag<br />ag<br />ag<br />ag<br />ag<br />B<br />B<br />B<br />High affinity<br />Avidity Index (AI)<br />Quantify strength of Ab binding<br />Concentration of urea required to displace 50% of flu-specific Abs<br />B<br />Low affinity<br />
    • 8. Results:All subjects<br />HAI<br />GMT<br />MN<br />GMT<br />Avidity<br />Avidity Index<br />
    • 9. HAI<br />Naive/Primedsubjects<br />GMT<br />Primed subjects with HAI >10 at V1<br />Naive = 55/73 (75%)<br />Primed = 18/73 (25%)<br />MN<br />GMT<br />Avidity<br />Avidity Index<br />
    • 10. Naive subjects<br />HAI<br />GMT<br />AI difference between V1-V2 or V2-V3 <0<br />Avidity<br />MN<br />*<br />*<br />GMT<br />Avidity Index<br /><ul><li>Naive AI+ : 44/55 (80%)
    • 11. Naive AI- : 11/55 (20%)</li></li></ul><li>HAI<br />Primedsubjects<br />GMT<br /><ul><li>AI difference between V1-V2 or V2-V3 <0</li></ul>MN<br />Avidity<br />GMT<br />Avidity Index<br /><ul><li>Primed AI+ : 9/18 (50%)
    • 12. Primed AI- : 9/18 (50%)</li></li></ul><li>Conclusions/Questions<br />Why is there a failure to increase antibody avidity following a second immunization?<br />20/73 = 27% of all subjects<br />11/55 = 20% of naive subjects with AI<br /> 9/18 = 50% of primed subjects with no change<br />Maturation of the humoral immune response was abnormally truncated<br />Effect of low antigen dose in adjuvanted vaccine?<br />Role of pre-existing immunity on the response to influenza vaccines?<br />
    • 13. Acknowledgements<br />Dr. Brian J. Ward<br />Dr. Jyotsana Gupta<br />Angela Brewer<br />Members of Ward lab<br /><ul><li>Dr. David Scheifele
    • 14. RT-03 investigators</li></li></ul><li>Influenza-specific IgG subclass<br />Visit 2<br />Avidity<br />*<br />*<br />*<br />Avidity Index<br />IgG1<br />IgG2<br />IgG3<br />IgG4<br />

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