Search

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).

Introduction: Pendant la pandémie d'influenza A/H1N1/09 nous avons comparé les taux d'anticorps induits par l'infection et par immunisation avec des vaccins pandémiques chez des enfants immunocompétents et immunosupprimés. Méthodes: Etude prospective enrôlant des enfants post-infection et post-vaccination avec 1 dose (immunocompétents) ou 2 doses (immunosupprimés) de vaccin adjuvanté (Pandemrix®/Focetria®). Les titres d'anticorps étaient mesurés 4-6 semaines postvaccination/maladie. Résultats: Chez les enfants immunocompétents, les anticorps induits par une dose (N=48, séroprotection 98%; titre moyen géométrique (GMT):395) étaient comparables à ceux de 51 enfants convalescents (séroprotection:98%; GMT:350). Les 27 enfants immunosupprimés, après 2 doses, atteignaient un taux de séroprotection (89%) et un titre moyen (GMT:306) légèrement plus bas. Les effets indésirables étaient plus fréquents/forts avec l'âge (P=0.01) et avec Pandemrix® comparé à Focetria® (P=0.03). Conclusions: Chez les enfants immunocompétents, une dose de vaccin était aussi immunogène que la maladie. Deux doses suffisaient pour protéger la plupart des enfants immunosupprimés.

We aimed to determine the antibody responses and effect on viral load of the AS03-adjuvanted pandemic H1N1 vaccine in HIV-infected patients.A total of 121 HIV-infected patients and 138 healthy subjects were enrolled in a prospective, open-label study. Healthy subjects received one dose and HIV-infected patients two doses of the AS03-adjuvanted split influenza A/09/H1N1 vaccine (Pandemrix®; GlaxoSmithKline, Brentford, United Kingdom.) at an interval of 3-4 weeks. The study was extended in 2010/2011 for 66 patients. Geometric mean titres (GMTs), seroprotection rates (post-vaccination titre ≥ 1:40) and HIV-1 RNA levels were measured before and 4 weeks after immunization.After two immunizations, the seroprotection rate (94.2 vs. 87%, respectively) and GMT (376 vs. 340, respectively) in HIV-infected patients were as high as in healthy subjects after one dose, regardless of CD4 cell count. Four weeks after immunization, HIV RNA was detected in plasma samples from 40 of 68 (58.0%) previously aviraemic patients [median 152 HIV-1 RNA copies/mL; interquartile range (IQR) 87-509 copies/mL]. Subsequent measures indicated that HIV RNA levels had again declined to20 copies/mL in most patients (27 of 34; 79.4%). Following (nonadjuvanted) influenza immunization in 2010/2011, HIV RNA levels only slightly increased (median final level 28 copies/mL) in three of 66 (4.5%) previously aviraemic patients, including two of 25 (8%) patients in whom an increase had been elicited by AS03-adjuvanted vaccine the year before.Most HIV-infected patients developed seroprotection after two doses of AS03-adjuvanted pandemic vaccine. A transient effect on HIV RNA levels was observed in previously aviraemic patients. A booster dose of the nonadjuvanted influenza vaccine containing the A/09/H1N1 strain the following year did not reproduce this finding, indicating a non-antigen-specific adjuvant effect.

Objective To identify the determinants of antibody responses to adjuvanted split influenza A (H1N1) vaccines in patients with inflammatory rheumatic diseases. Methods One hundred seventy-three patients (82 with rheumatoid arthritis, 45 with spondylarthritis, and 46 with other inflammatory rheumatic diseases) and 138 control subjects were enrolled in this prospective single-center study. Controls received 1 dose of adjuvanted influenza A/09/H1N1 vaccine, and patients received 2 doses of the vaccine. Antibody responses were measured by hemagglutination inhibition assay before and 3–4 weeks after each dose. Geometric mean titers (GMTs) and rates of seroprotection (GMT ≥40) were calculated. A comprehensive medical questionnaire was used to identify the determinants of vaccine responses and adverse events. Results Baseline influenza A/09/H1N1 antibody levels were low in patients and controls (seroprotection rates 14.8% and 14.2%, respectively). A significant response to dose 1 was observed in both groups. However, the GMT and the seroprotection rate remained significantly lower in patients (GMT 146 versus 340, seroprotection rate 74.6% versus 87%; both P < 0.001). The second dose markedly increased antibody titers in patients, with achievement of a similar GMT and seroprotection rate as elicited with a single dose in healthy controls. By multivariate regression analysis, increasing age, use of disease-modifying antirheumatic drugs (DMARDs) (except hydroxychloroquine and sulfasalazine), and recent (within 3 months) B cell depletion treatment were identified as the main determinants of vaccine responses; tumor necrosis factor α antagonist treatment was not identified as a major determinant. Immunization was well tolerated, without any adverse effect on disease activity. Conclusion DMARDs exert distinct influences on influenza vaccine responses in patients with inflammatory rheumatic diseases. Two doses of adjuvanted vaccine were necessary and sufficient to elicit responses in patients similar to those achieved with 1 dose in healthy controls.