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The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines Karen K. Yam, Ph.D. Post-doctoral Fellow (Brian Ward Lab) PCIRN Annual Meeting Wednesday April 20th, 2011
Objectives Understand the influence of adjuvants on long-term humoral responses to influenza following vaccination PCIRN RT-03 Study Canadian pH1N1 influenza vaccine ASO3 adjuvant 25% of the antigen dose of regular vaccine Hypothesis Low dose of antigen in adjuvanted vaccine may enhance the short-term response at the expense of the long-term immunity
PCIRN RT-03 Study 167 pediatric subjects (6-35 months) Arepanrix vaccine ASO3-adjuvanted pH1N1(2009) Visit 1 Visit 2 Visit 3 Day: 0 21 42 80% seroprotected 100% seroprotected
Methods:Sample selection RT-03 serum samples in the PCIRN archive Selected: All 3 timepoints available V1, V2, V3 73 subjects selected
Methods:Serum Analysis Hemagglutination Inhibition (HAI) assay Titer of flu-specific Abs National Microbiology Laboratory Micro-neutralization (MN) assay Titer of functional Abs that can neutralize viral entry Avidity Index ELISA Measure of the binding strength of flu-specific Ab Read-out for the development of humoralimmresp
Affinity/Avidity Maturation Humoral immune response B ag B cell Antibodies
Affinity/Avidity Maturation B B B B ag ag ag ag ag ag ag ag B B B High affinity Avidity Index (AI) Quantify strength of Ab binding Concentration of urea required to displace 50% of flu-specific Abs B Low affinity
Results:All subjects HAI GMT MN GMT Avidity Avidity Index
HAI Naive/Primedsubjects GMT Primed subjects with HAI >10 at V1 Naive = 55/73 (75%) Primed = 18/73 (25%) MN GMT Avidity Avidity Index
Naive subjects HAI GMT AI difference between V1-V2 or V2-V3 <0 Avidity MN * * GMT Avidity Index ,[object Object]
Naive AI-  : 11/55 (20%),[object Object]
Primed AI-  : 9/18 (50%),[object Object]
Acknowledgements Dr. Brian J. Ward Dr. Jyotsana Gupta Angela Brewer Members of Ward lab ,[object Object]
RT-03 investigators,[object Object]

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

  • 1. The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines Karen K. Yam, Ph.D. Post-doctoral Fellow (Brian Ward Lab) PCIRN Annual Meeting Wednesday April 20th, 2011
  • 2. Objectives Understand the influence of adjuvants on long-term humoral responses to influenza following vaccination PCIRN RT-03 Study Canadian pH1N1 influenza vaccine ASO3 adjuvant 25% of the antigen dose of regular vaccine Hypothesis Low dose of antigen in adjuvanted vaccine may enhance the short-term response at the expense of the long-term immunity
  • 3. PCIRN RT-03 Study 167 pediatric subjects (6-35 months) Arepanrix vaccine ASO3-adjuvanted pH1N1(2009) Visit 1 Visit 2 Visit 3 Day: 0 21 42 80% seroprotected 100% seroprotected
  • 4. Methods:Sample selection RT-03 serum samples in the PCIRN archive Selected: All 3 timepoints available V1, V2, V3 73 subjects selected
  • 5. Methods:Serum Analysis Hemagglutination Inhibition (HAI) assay Titer of flu-specific Abs National Microbiology Laboratory Micro-neutralization (MN) assay Titer of functional Abs that can neutralize viral entry Avidity Index ELISA Measure of the binding strength of flu-specific Ab Read-out for the development of humoralimmresp
  • 6. Affinity/Avidity Maturation Humoral immune response B ag B cell Antibodies
  • 7. Affinity/Avidity Maturation B B B B ag ag ag ag ag ag ag ag B B B High affinity Avidity Index (AI) Quantify strength of Ab binding Concentration of urea required to displace 50% of flu-specific Abs B Low affinity
  • 8. Results:All subjects HAI GMT MN GMT Avidity Avidity Index
  • 9. HAI Naive/Primedsubjects GMT Primed subjects with HAI >10 at V1 Naive = 55/73 (75%) Primed = 18/73 (25%) MN GMT Avidity Avidity Index
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Editor's Notes

  1. The Immunobiology of Oil-in-Water Adjuvants for Influenza Vaccines
  2. 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...
  3. 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.
  4. Geometric mean with 95% confidence intervalof HAI, MN, Avidity ELISAs