Prior Receipt of 2008-09 Trivalent Inactivated Influenza Vaccine Increases Pandemic H1N1 Severity In Ferrets:

Randomized Double-blind Placebo-controlled Experiment

Presentation Abstract
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
Pres. Time: Sunday, Sep 09, 2012
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. 

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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