Influence of Statins on Influenza Vaccine Response in Elderly Individuals

n/

A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59®-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration

Strategies to optimize responses to seasonal influenza vaccination in older adults include the use of adjuvants, higher antigen doses, and intradermal delivery. In this study adults aged >= 65 years (n = 450) received a single dose of 1 of 2 non-adjuvanted trivalent influenza vaccine (TIV) formulations administered intradermally (ID), both containing 6 mu g of A/H1N1 and B, differing in A/H3N2 content (6 mu g or 12 mu g), or a single dose of 1 of 8 TIV formulations administered intramuscularly (IM) all containing 15 mu g of A/H1N1 and B, differing in A/H3N2 hemagglutinin (HA) content (15 mu g or 30 mu g) and/or in MF59 (R) adjuvant content (0%, 25%, 50%, or 100% of the standard dose). This paper focuses on the comparisons of low-dose non-adjuvanted ID, full-dose non-adjuvanted IM and full-dose MF59-adjuvanted IM formulations (n = 270). At day 22 post-vaccination, at least one European licensure immunogenicity criterion was met by all groups against all 3 strains; however, all three criteria were met against all 3 vaccine strains by the low-dose non-adjuvanted ID and the full-dose MF59-adjuvanted IM groups only. The full-dose MF59-adjuvanted IM group elicited significantly higher immune response vs. the low-dose non-adjuvanted ID formulations for most comparisons. The full-dose MF59 adjuvanted IM groups were associated with increased pain at the site of injection (P < 0.01) compared to the ID groups, and the low-dose non-adjuvanted ID groups were associated with increased erythema, induration, and swelling at the injection site (P < 0.0001) and unsolicited AEs compared with the IM groups. There were no differences between IM and ID groups in the frequencies of subjects experiencing solicited systemic reactions. Overall, while MF59 adjuvantation increased pain at the site of injection, and intradermal delivery increased unsolicited adverse events, erythema, induration, and swelling at the injection site, both strategies of vaccination strongly enhanced the immunogenicity of seasonal influenza vaccine in older adults compared with conventional non-adjuvanted intramuscular delivery

Health-related quality of life, treatment satisfaction and clinical aspects of patients with primary antibody deficiency receiving subcutaneous IgG self-infusions at home

Patients with primary antibody deficiencies (PAD) are unable to produce sufficient amounts of antibodies and are therefore susceptible to severe bacterial infections. The standard therapy has been intravenous infusions of immunoglobulin G (IVIG) every 2-4 weeks. While this treatment has proved to be effective and safe, it is cumbersome for patients: it may be difficult to find venous access, and they have to visit the hospital regularly to deal with repeated IVIG infusions. IgG serum levels are not stable between infusions. Rapid subcutaneous immunoglobulin G (SCIG) self-infusions provide a suitable alternative that has an excellent safety and efficacy profile, is easy, and can be performed at home. As IVIG and SCIG replacement therapies are both equally effective, patient-reported outcomes (PRO) such as health-related quality of life (HRQL), and treatment satisfaction (TS) may be used as criteria for an evidence-based choice of treatment alternatives. Studies investigating the infection experience of paediatric and adult PAD patients, as well as data addressing the HRQL and TS of PAD patients, have been rare or even non-existent. Some questionnaires used to capture PRO data have never been used or validated in PAD patients. For the present project two prospective multinational studies were conducted in PAD patients, one in Europe and Brazil, and another one in the USA and Canada, with the following objectives: to study the safety and efficacy of rapid SCIG self-infusions at home (adults, children); to compare IVIG replacement therapy in the hospital or at home and SCIG self-infusions at home with regard to PRO measures (HRQL: SF-36 for adults, CHQPF50 for children; TS: LQI for adults and children); and to examine validation aspects of the instruments used to assess HRQL and TS. Once they had switched from IVIG to SCIG therapy, IgG levels increased in children and remained constant in adults. Only one serious infection (pneumonia) occurred, and the rate of systemic adverse reactions, mainly mild, amounted to 1% of the infusions. Twenty-eight percent of the infusions were followed by mostly mild, local, transient tissue reactions which required no treatment and declined over time. Parents reported significant improvements related to their children's social functioning and health, the parents' own life situation and the way the family functioned. There was significant improvement on the SF-36 Mental Health and Social Functioning scales in the European study, and on the Role Physical, General Health and Health Transition scales in the North American study. The Vitality scale improved significantly in both studies. For patients on IVIG at hospital at enrolment, SCIG home therapy resulted in greater independence, with less disruption of daily activities, less impact on school, work and social activities, freedom to travel, better therapy convenience, comfort, treatment flexibility and pleasantness of treatment atmosphere. Patients who had received IVIG at home at study enrolment reported improved health status. Almost all adult and paediatric patients/caregivers preferred home treatment, and a great majority, even those who had been satisfied with IVIG at home, preferred subcutaneous self-infusions. The LQI could be broken down into four factors, relating to treatment interference with daily life activities, therapy-related problems, therapy setting and costs. To conclude, the studies have shown that SCIG self-infusions at home are not only effective and safe, but adults, children and their caregivers appreciate this method. HRQL is significantly improved and a marked improvement in TS gives the patients and their families greater independence and flexibility

Trivalent and quadrivalent MF59(®)-adjuvanted influenza vaccine in young children : a dose- and schedule-finding study.

Young children are at increased risk for influenza infections and related complications. The protection offered to children by conventional trivalent inactivated influenza vaccines (TIV) is suboptimal, due to poor immunogenicity and a higher exposure to infection and complications in this age group, particularly from influenza B strains. In this dose-ranging, factorial design trial, we report the safety and immunogenicity of different combinations of adjuvanted (ATIV) and non-adjuvanted trivalent (TIV) and quadrivalent (QIV) influenza vaccines in 480 healthy children 6 to <36 months of age. The results show that the second B strain added to TIV was immunogenic and did not affect immunogenicity of the other strains. The addition of the MF59(®) adjuvant promoted robust immune responses with notable elevations in antibodies observed even after one dose. A dose-response relationship was observed between the antibody response and MF59 adjuvant. No patterns in safety and tolerability emerged with different adjuvant and antigen doses nor with the addition of a second B strain. MF59-adjuvanted QIV offers potential advantages to young children

Safety of MF59-adjuvanted versus non-adjuvanted influenza vaccines in children and adolescents : an integrated analysis.

We reviewed the safety of MF59-adjuvanted versus non-adjuvanted influenza vaccines in children and adolescents (aged 6 months-18 years) in an integrated analysis of all pediatric trials evaluating MF59-containing influenza vaccines completed to date (5 trials). In the MF59-adjuvanted group (n=1181) versus the non-adjuvanted group (n=545) there was no increase in the incidence of unsolicited adverse events and serious adverse events. As expected, solicited local or systemic reactions occurred more frequently in MF59-adjuvanted subjects; however, a majority of reactions were mild and transient. These data support the safety of MF59-adjuvanted influenza vaccines in the pediatric population

Superior immunogenicity of seasonal influenza vaccines containing full dose of MF59® adjuvant: results from a dose-finding clinical trial in older adults

Background: MF59-adjuvanted influenza vaccines have superior immunogenicity in older adults compared with non-adjuvanted vaccines. We assessed whether changing formulation (i.e., increasing H3N2 antigen or decreasing the quantity of adjuvant) of the licensed, MF59-adjuvanted trivalent influenza subunit vaccine Fluad(R) (Novartis Vaccines and Diagnostics) improves the risk-benefit profile in vaccinees aged >65 years. Results: A significant dose-response relationship was observed between antibody levels and MF59 dose; full dose formulations elicited the strongest immune responses, meeting immunogenicity licensure criteria by Day 8. Doubling H3N2 antigen content did not increase the response to this antigen. Increased frequency of circulating CD4+ T-cells specific for vaccine antigens were detected by Day 8; magnitude and functional profile of the CD4+ T-cell response was comparable across the different vaccination groups. Mild to moderate solicited local reactions were more common with vaccines formulated with higher doses of MF59(R), but there were no MF59- or antigen dose-related increase in the frequency of solicited systemic reactions or unsolicited adverse events and serious adverse events. Methods: We report on 357 subjects who received one of eight intramuscular vaccine formulations. Hemagglutination-inhibiting antibodies were assayed on Days 1, 8 and 22; magnitude and functional profile of CD4+ T-cell responses to vaccine antigens were assessed in subsets. Solicited adverse reactions were reported via diary cards for seven days after vaccination and spontaneous adverse events were monitored throughout the study. Conclusion: This study confirms that the current formulation is the optimal one for MF59-adjuvanted influenza vaccine for use in older adults

Primary cutaneous diffuse large B-cell lymphoma, NOS and leg type: Clinical, morphologic and prognostic differences

Background and objectives : Primary cutaneous diffuse large B-cell lymphoma, NOS (PCLBCL/NOS) is a rare PCLBCL. Only few data are available for this tumor. The aim of this study was to identify clinical and/or immunohistochemical markers (in addition to Bcl-2) that characterize PCLBCL/NOS, assist in differentiating it from PCLBCL, leg type (PCLBCL/LT) and help to assess the clinical course/prognosis. Patients and methods : Bcl-2 -PCLBCL/NOS) cases (n = 14 were compared with Bcl-2(+) PCLBCL/LT cases (n = 29). Results : PCLBCL/NOS patients were younger, predominantly male and had better survival rates than patients with PCLBCL/LT. Patients with PCLBCL/NOS presented more often with larger plaques limited to one or two contiguous body regions, whereas PCLBCL/LT cases often presented with disseminated lesions. Neoplastic cells had a higher proliferation rate (Ki67) in PCLBCL/LT patients. The tumor microenvironment of PCLBCL/NOS had a more prominent CD3 + infiltrate. Overall survival data for the whole cohort (n = 37) revealed that female gender and Bcl-2 expression correlated with a worse survival rate. Bcl-6 expression and centroblastic subtype correlated with better outcomes. None of the other markers studied (e. g. GCB/non-GCB subtype) correlated with survival rate. Conclusions : PCLBCL/NOS and PCLBCL/LT differ in their clinical behavior and outcomes. Bcl-2 still seems to be the best marker for discriminating between these two subgroups. Bcl-2, female gender and Bcl-6 represent prognostic markers for PCLBCL