Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host

Lavallade, Hugues de; Garland, Paula; Sekine, Takuya; Höschler, Katja; Marín, David; Stringaris, Kate; Loucaides, Eva; Howe, Katherine; Szydlo, Richard; Kanfer, Ed; Macdonald, Donald; Kelleher, Peter; Cooper, Nichola; Khoder, Ahmad; Gabriel, Ian; Milojković, Dragana; Pavlů, Jiří; Goldman, John M.; Apperley, Jane F.; Rezvani, Katayoun

doi:10.3324/haematol.2010.032664

Cited by 118 publications

(129 citation statements)

References 31 publications

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“…31 Recently, Issa et al 32 observed modest rates of seroprotective titers (51.2%) in HSCT recipients after one dose of vaccine. Our study shows that 2 doses of an adjuvanted vaccine were much more effective than a single dose, confirming the results of De Lavallade et al 22 who demonstrated in a smaller cohort of 22 HSCT recipients that seroprotection was significantly boosted by a second dose of the AS03-adjuvanted vaccine. The very low incidence of confirmed H1N1/A/09 infections (4.6%), all of which occurred within two weeks after the first dose, confirms that 2 doses may have induced a protective immunity against H1N1/A/09 in our patient population.…”

Section: Discussionsupporting

confidence: 81%

“…7,[21][22][23]25,34,35 Our results confirm that this remains the case even when more potent adjuvanted vaccines are used. Furthermore, we confirm that the type of conditioning has little impact.…”

Section: Discussionsupporting

confidence: 77%

“…Furthermore, we confirm that the type of conditioning has little impact. As reported by others, 22,32 we found no significant differences in responses between RIC and B. Mohty et al 902 haematologica | 2011; 96(6) MAC patients, probably reflecting similar long-term immune reconstitution after both conditioning regimens. 36 Ageing is known to affect humoral responses.…”

Section: Discussionsupporting

confidence: 62%

“…Actually, adverse events in our study were similar to those of healthy controls and we did not observe any triggering or exacerbation of GvHD, similar to other reports. 22,33 Obviously, due to the relatively small size of our cohort, these results must be interpreted with caution.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23][24][25] However, these were often limited by their small size and confounded by heterogeneous baseline influenza immunity, with pre-vaccination seroprotection rates ranging from 12% to 92%. 21,[23][24][25] Also, vaccine…”

Section: Discussionmentioning

confidence: 99%

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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

Mohty

Bel²,

Vukicevic³

et al. 2011

Haematologica

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BackgroundResponses 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 MethodsWe 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. ResultsBaseline 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 12g/L, lymphopenia less than1G/L, IgG less than 4g/L, IgA less than 0.5g/L, IgM less than 0.5g/L and naive CD4 + T cells less than 150/mL 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. ConclusionsIn 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. 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

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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

Mohty

Bel²,

Vukicevic³

et al. 2011

Haematologica

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Influenza vaccines in immunosuppressed adults with cancer

Eliakim‐Raz

Vinograd

Trestioreanu

et al. 2013

Cochrane Database of Systematic Reviews

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Background Immunosuppressed cancer patients are at increased risk of serious influenza-related complications. Guidelines, therefore, recommend influenza vaccination for these patients. However, data on vaccine effectiveness in this population is lacking, and the value of vaccination in this population remains unclear. Objectives To assess the effectiveness of influenza vaccine in immunosuppressed adults with malignancies. The primary review outcome is allcause mortality, preferably at the end of the influenza season. Influenza-like illness (ILI, a clinical definition), confirmed influenza, pneumonia, any hospitalization and influenza-related mortality were defined as secondary outcomes. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS databases up to August 2013. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (hematological), and ASCO (oncological) between the years 2006 to 2010. In addition, we scanned the references of all identified studies and pertinent reviews. We searched the websites of the manufacturers of influenza vaccine. Finally, we searched for ongoing or unpublished trials in clinical trial registry databases using the website. Selection criteria Randomized controlled trials (RCTs), prospective and retrospective cohort studies and case-control studies were considered, comparing inactivated influenza vaccines versus placebo, no vaccination or a different vaccine, in adults (16 years and over) with cancer. We considered solid malignancies treated with chemotherapy, haematological cancer patients treated or not treated with chemotherapy, cancer patients post-autologous (up to six months after transplantation) or allogeneic (at any time) hematopoietic stem cell transplantation. Data collection and analysis Two review authors independently assessed the risk of bias and extracted data from included studies adhering to Cochrane methodology. Meta-analysis could not be performed because of different outcome and denominator definitions in the included studies.

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