Yerly, Y. improving. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons. Results Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. Conclusions Priming with 2 doses of Pandemrix? elicited prolonged antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in Belotecan hydrochloride HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients. Trial Registration ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT01022905″,”term_id”:”NCT01022905″NCT01022905 Introduction Immunosuppressed patients are at higher risks of influenza complications. This was evidenced by reports of disease end result in solid organ transplant (SOT) recipients infected by the pandemic influenza A/09/H1N1 strain [1]C[6]. A similar risk exists in HIV infected individuals with advanced disease and low CD4 cell count but not in HAART-treated patients [7]C[11]. Immunosuppressed patients have a general pattern toward impaired antibody responses to non-adjuvanted vaccines [6]. Short-term antibody responses were indeed lower following 1 or 2 2 doses of non-adjuvanted influenza A/09/H1N1 vaccines in HIV-infected [12], [13] and solid organ transplant (SOT) patients [13]C[15]. The extent to which adjuvanted vaccines may improve responses is usually thus of central interest. In HIV-infected patients, a single dose of the AS03-adjuvanted pandemic vaccine (Pandemrix?) elicited higher responses than non-adjuvanted monovalent vaccines [16]. Four weeks after 1 dose of Pandemrix?, seroresponses remained lower than in controls [17], [18] reaching comparable titers after 2 doses [19]C[21]. Seroresponses remained lower in SOT recipients even after 2 doses of Pandemrix? [19], [22], [23], reflecting a more profound impact of immunosuppression on vaccine responses. How immunosuppression affects memory responses is usually less well defined. In HIV-infected patients, impaired B and T cell functions cause dysfunctional germinal center interactions [24] and result in a progressive loss of B-cell memory despite antiretroviral therapy [25]C[27]. Accordingly, most HAART-treated HIV-infected adults reached a hemagglutination inhibition titer (HAI) 1/40 four weeks after immunization with non-adjuvanted A/09/H1N1 vaccines but only 28% remained above this threshold at 6 months [28]. How the immunosuppression of SOT patients affects memory responses is usually less well explained. In 2009/2010, we had followed 760 immunocompromised and 133 healthy adults immunized with 1 (healthy) or 2 (patients) doses of Pandemrix?. Four weeks after immunization, we observed similar responses in HIV-infected individuals after 2 doses Belotecan hydrochloride as in healthy adults after 1 dose [20], and lower seroresponses in SOT recipients despite 2 immunizations [23]. To define how adjuvanted vaccines would influence antibody persistence and memory responses, we assessed the impact of 2009/2010 priming with Pandemrix? on antibody persistence and memory responses elicited in 2010/2011 by one dose of a non-adjuvanted trivalent inactivated seasonal vaccine including the same influenza A/09/H1N1 strain. Patients and Methods Subjects This prospective, multisite, open-label study recruited 406 subjects in November 2010197 HIV-infected patients, 53 SOT (kidney) recipients and 156 healthy controls (HC) (Physique S1). Inclusion criteria included age above 18 years and having received 1 (controls) or 2 (patients) doses of AS03-adjuvanted pandemic influenza vaccine in 2009/2010. Among these 406 subjects, 191 subjects (69 HIV-infected patients, 51 kidney transplant recipients and 71 controls) had already been enrolled in 2009/2010 and were followed for 2 seasons. The latter are referred to as the 2009C2010C2011 cohort. The study was approved by the institutional review table (ID: CER-09-234), registered on ClinicalTrials.gov prior to patient enrolment (ID: “type”:”clinical-trial”,”attrs”:”text”:”NCT01022905″,”term_id”:”NCT01022905″NCT01022905) and conducted in accordance with the principles of the Declaration of Helsinki, the requirements of Good Clinical Practice, and Swiss regulatory requirements. Written informed consent was obtained prior to inclusion in 2009 2009 and in 2010 2010. The protocol for this trial is usually available as supporting information, see Protocol S1. Vaccines and Immunizations In 2010/2011, patients and controls received one intramuscular dose of a non-adjuvanted trivalent split-virus influenza vaccine made up of 15 g of A/California/07/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008. Most patients ( 98% in each group) received Mutagrip? (SanofiPasteurMSD). TNFSF13 In 2009/2010, all participants experienced received 1 (healthy controls) or 2 doses (HIV-infected or Belotecan hydrochloride SOT patients) of AS03-adjuvanted split-virus influenza A/09/H1N1 vaccine (Pandemrix?, GlaxoSmithKline) at a 4 weeks interval, according to standard Swiss recommendations. Each dose of Pandemrix? contained 3.75 g of.