Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients
Bilal Mohty, Michael Bel, Marija Vukicevic, Monika Nagy, Emmanuel Levrat, Sara Meier, Stephane Grillet, Christophe Combescure, Laurent Kaiser, Yves Chalandon, Jakob Passweg, Claire-Anne Siegrist, Eddy Roosnek, Blood and Marrow Transplant Program, Geneva University Hospitals H1N1 study group, C A Siegrist, K Posfay-Barbe, S Meier, M Bel, S Grillet, G Sealy, S Charvat, J Demeules, M Verdon, C Combescure, B Hirschel, A Calmy, A Nguyen, C Delhumeau-Cartier, J Ambrsioni, C Gabay, P A Guerne, J Seebach, C Ribi, J Villard, P Y Dietrich, A C George, L Favet, C van Delden, I Morard, G Mentha, E Giostra, K Hadaya, P Y Martin, P Soccal, T Berney, S Noble, B Mohty, M Nagy, Y Chalandon, E Roosnek, J Passweg, L Kaiser, S Yerly, Y Thomas, W Wunderli, Bilal Mohty, Michael Bel, Marija Vukicevic, Monika Nagy, Emmanuel Levrat, Sara Meier, Stephane Grillet, Christophe Combescure, Laurent Kaiser, Yves Chalandon, Jakob Passweg, Claire-Anne Siegrist, Eddy Roosnek, Blood and Marrow Transplant Program, Geneva University Hospitals H1N1 study group, C A Siegrist, K Posfay-Barbe, S Meier, M Bel, S Grillet, G Sealy, S Charvat, J Demeules, M Verdon, C Combescure, B Hirschel, A Calmy, A Nguyen, C Delhumeau-Cartier, J Ambrsioni, C Gabay, P A Guerne, J Seebach, C Ribi, J Villard, P Y Dietrich, A C George, L Favet, C van Delden, I Morard, G Mentha, E Giostra, K Hadaya, P Y Martin, P Soccal, T Berney, S Noble, B Mohty, M Nagy, Y Chalandon, E Roosnek, J Passweg, L Kaiser, S Yerly, Y Thomas, W Wunderli
Abstract
Background: Responses to influenza vaccines are poorly characterized in immunocompromised patients. The goal of this study was to assess the efficacy of the AS03-adjuvanted influenza H1N1/A/09 vaccine in allogeneic hematopoietic stem cell transplant recipients.
Design and methods: We enrolled 65 patients and 138 controls in an open prospective study. Controls received one dose and patients 2 doses of the AS03-adjuvanted influenza H1N1/A/09 vaccine at a 3-week interval. Geometric mean titers and seroprotection/seroconversion rates were determined by hemagglutination inhibition before and four weeks after the last immunization. Clinical and biological markers, including immunoglobulins, CD3+, CD4+, CD8+ and naïve CD4+ T-cell counts were assessed in all patients.
Results: Baseline seroprotection rates were low in patients (6.6%) and controls (14.8%). After 2 doses, patients (n=57, 92.3%) achieved similar seroprotection rates (84% vs. 87%, P=0.65) and antibody titers (305 vs. 340, P=0.88) as controls (n=131, 93.9%) after one dose. In univariate analysis, transplant-to-vaccination interval less than 12 months, active graft-versus-host disease, immunosuppressive drugs, hemoglobin less than 12 g/L, lymphopenia less than 1 G/L, IgG less than 4 g/L, IgA less than 0.5 g/L, IgM less than 0.5 g/L and naive CD4+ T cells less than 150/μL were significantly associated with weaker responses. Multivariate analysis identified transplant-to-vaccination interval and active graft-versus-host disease as the most powerful negative predictors of antibody responses (P=0.04 and P=0.002, respectively). Vaccination was well tolerated in both cohorts.
Conclusions: In allogeneic hematopoietic stem cell transplant recipients, 2 doses of an adjuvanted influenza vaccine elicited comparable responses to a single dose in healthy individuals. However, vaccine responses remained poor in patients with ongoing graft-versus-host disease, supporting the need for additional strategies in this high-risk patient population. (ClinicalTrials.gov Identifier: NCT01022905).
Figures
Source: PubMed