Giuseppe
Emeritus
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
Open Access / Peer-Reviewed / Research Article
Randomized Controlled Ferret Study to Assess the Direct Impact of 2008?09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk
Danuta M. Skowronski, Marie-Eve Hamelin, Gaston De Serres, Naveed Z. Janjua, Guiyun Li, Suzana Sabaiduc, Xavier Bouhy, Christian Couture, Anders Leung, Darwyn Kobasa, Carissa Embury-Hyatt, Erwin de Bruin, Robert Balshaw, [ ... ], Sophie Lavigne, Martin Petric, Marion Koopmans, Guy Boivin
Published: January 27, 2014 / DOI: 10.1371/journal.pone.0086555
Abstract
During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008?09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008?09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008?09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-na?ve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-na?ve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008?09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.
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Citation: Skowronski DM, Hamelin M-E, De Serres G, Janjua NZ, Li G, et al. (2014) Randomized Controlled Ferret Study to Assess the Direct Impact of 2008?09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk. PLoS ONE 9(1): e86555. doi:10.1371/journal.pone.0086555
Editor: Suryaprakash Sambhara, Centers for Disease Control and Prevention, United States of America
Received: September 12, 2013; Accepted: December 17, 2013; Published: January 27, 2014
Copyright: ? 2014 Skowronski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grants provided by the Michael Smith Foundation for Health Research (OT-GIA-00012091) and the Canadian Institutes of Health Research - Institute of Infection and Immunity (229733). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have the following conflicts: Gaston De Serres has received research grants from GSK and Sanofi Pasteur and received reimbursement for travel fee to attend a GSK ad hoc Advisory board meeting. Guy Boivin has received research grants from GSK and Medicago. Marion Koopmans and Erwin de Bruin have received grants from the Dutch government, from the Wellcome trust, and from the European commission. Before joining the BC Centre for Disease Control, Robert Balshaw was previously (within the last 36 months) Director of Biometrics for Syreon Corporation, a contract research organization which has conducted clinical trials on behalf of pharmaceutical companies. The other authors declare that they have no conflicts of interest to report. This does not alter the authors? adherence to all PLOS ONE policies on sharing data and materials.
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Open Access / Peer-Reviewed / Research Article
Randomized Controlled Ferret Study to Assess the Direct Impact of 2008?09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk
Danuta M. Skowronski, Marie-Eve Hamelin, Gaston De Serres, Naveed Z. Janjua, Guiyun Li, Suzana Sabaiduc, Xavier Bouhy, Christian Couture, Anders Leung, Darwyn Kobasa, Carissa Embury-Hyatt, Erwin de Bruin, Robert Balshaw, [ ... ], Sophie Lavigne, Martin Petric, Marion Koopmans, Guy Boivin
Published: January 27, 2014 / DOI: 10.1371/journal.pone.0086555
Abstract
During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008?09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008?09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008?09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-na?ve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-na?ve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008?09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.
____
Citation: Skowronski DM, Hamelin M-E, De Serres G, Janjua NZ, Li G, et al. (2014) Randomized Controlled Ferret Study to Assess the Direct Impact of 2008?09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk. PLoS ONE 9(1): e86555. doi:10.1371/journal.pone.0086555
Editor: Suryaprakash Sambhara, Centers for Disease Control and Prevention, United States of America
Received: September 12, 2013; Accepted: December 17, 2013; Published: January 27, 2014
Copyright: ? 2014 Skowronski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grants provided by the Michael Smith Foundation for Health Research (OT-GIA-00012091) and the Canadian Institutes of Health Research - Institute of Infection and Immunity (229733). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have the following conflicts: Gaston De Serres has received research grants from GSK and Sanofi Pasteur and received reimbursement for travel fee to attend a GSK ad hoc Advisory board meeting. Guy Boivin has received research grants from GSK and Medicago. Marion Koopmans and Erwin de Bruin have received grants from the Dutch government, from the Wellcome trust, and from the European commission. Before joining the BC Centre for Disease Control, Robert Balshaw was previously (within the last 36 months) Director of Biometrics for Syreon Corporation, a contract research organization which has conducted clinical trials on behalf of pharmaceutical companies. The other authors declare that they have no conflicts of interest to report. This does not alter the authors? adherence to all PLOS ONE policies on sharing data and materials.
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