Presentation Abstract

Session: 030-Non HIV Virology
Sunday, Sep 09, 2012, 11:30 AM - 1:30 PM
Presentation Title: V-400d - Prior Receipt of 2008-09 Trivalent Inactivated Influenza Vaccine Increases Pandemic H1N1 Severity In Ferrets: Randomized Double-blind Placebo-controlled Experiment
Location: Halls A-C
Presentation Number: V-400d
Pres. Time: Sunday, Sep 09, 2012, 11:30 AM - 1:30 PM
Category: V
Keywords: Influenza vaccine ; influenza A ; Swine Influenza 
Author(s): D. M. Skowronski, MD, FRCPC - Prof1, M. E. Hamelin, PhD - Prof 2, G. De Serres, MD, PhD - Prof 3, N. Z. Janjua, MBBS, DrPH - Prof 1, G. Li, MPH, MSc - Analyst 1, X. Bouhy, BSc - Technician 2, C. Couture, MD, MSc - Prof 4, S. Lavigne, MSc - Pathologist 4, G. Boivin, MD - Prof 2;
1BC Ctr. for Disease Control, Vancouver, Canada, 2Ctr. Hosp.ier Universitaire de Québec, Québec, Canada, 3Institut national de santé publique du Québec, Québec, Canada, 4Institut universitaire de cardiologie et pneumologie de Québec, Québec, Canada.
Financial Disclosures:  D. M. Skowronski, None..
M. E. Hamelin, None. 
G. De Serres,
GSK Role(s): Research Contractor.
Sanofi Pasteur Role(s): Research Contractor.
N. Z. Janjua, None..
G. Li, None..
X. Bouhy, None..
C. Couture, None..
S. Lavigne, None. 
G. Boivin,
GSK Role(s): Research Contractor.
Abstract: Background: Observational studies from Canada reported increased risk of medically-attended A(H1N1)pdm09 illness in prior recipients of 2008-09 trivalent inactivated influenza vaccine (TIV). We used a ferret model to assess whether 2008-09 TIV directly influenced A(H1N1)pdm09 risk. Methods: In a double-blind study, 32 ferrets were randomly assigned to receive 500µL IM injections of 2008-09 Fluviral (GrpVac) or placebo (GrpPlac) on days 0, 28. On day 49, animals were challenged (Ch0) intranasally with 250µL (4.5logTCID50/mL) of A(H1N1)pdm09, half-volume per nares. Four ferrets/group were randomly selected for sacrifice day 54 (Ch+5) and the rest followed until sacrifice day 63 (Ch+14). Clinical characteristics were recorded pre-challenge then post-challenge until sacrifice. Virus titres were assessed in nasal wash pre-challenge then daily post-challenge until sacrifice, and in lungs at sacrifice. Lung inflammation was graded on six indicators each scored as 0 (none) to 3 (severe). Results: Baseline indicators, including weight (GrpVac: 0.96kg; GrpPlac: 0.97kg; p=0.87), were comparable. Beginning at Ch+2, GrpVac lost significantly more weight daily from baseline than GrpPlac, reaching the greatest between-group difference in percentage weight loss at Ch+5 (7.4% vs. 5.2%; p=0.02). Nasal virus titres did not differ significantly but rose more steeply between Ch+1-2 in GrpVac. At Ch+5, GrpVac had significantly higher lung virus titres than GrpPlac (logmean 4.96 vs. 4.23 pfu/mL; p=0.01) and higher combined lung pathology score (mean 5.75 vs. 2.13; p=0.3). Differences were no longer evident by Ch+14. Antibody and lung cytokine results will be available early fall, 2012. Conclusions: In ferrets, prior receipt of 2008-09 TIV increased A(H1N1)pdm09 severity. Immunologic mechanisms remain to be determined.

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