Immunogenicity and safety of different dose schedules and antigen doses of an MF59-adjuvanted H7N9 vaccine in healthy adults aged 65 years and older

BackgroundThe number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults.Methods479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose.ResultsSubjects in all groups had only modest immune responses, with the HAI GMT < 20 after the second vaccine dose and <29 after the third vaccine dose. HAI titers ≥ 40 were seen in <37% of subjects after the second dose and <49% after the third dose. There were no significant differences seen between the two dose schedules. MN titers followed similar patterns, although the titers were approximately two-fold higher than the HAI titers. Logistic regression modeling demonstrated no statistically significant associations between the immune responses and age, sex or body mass index whereas recent prior receipt of seasonal influenza vaccine significantly reduced the HAI response [OR 0.13 (95% CI 0.05, 0.33); p < 0.001]. Overall, the vaccine was well tolerated. Two mild potentially immune mediated adverse events occurred, lichen planus and guttate psoriasis.ConclusionsMF59-adjuvanted H7N9 IIV was only modestly immunogenic in the older adult population following three doses. There were no significant differences in antibody responses noted among the various antigen doses or the two dose schedules.     

Efficacy and safety of ruxolitinib in intermediate‐1 IPSS risk myelofibrosis patients: Results from an independent study

Patients with myelofibrosis at intermediate‐1 risk according to the International Prognostic Score System are projected to a relatively long survival; nonetheless, they may carry significant splenomegaly and/or systemic constitutional symptoms that hamper quality of life and require treatment. Since registrative COMFORT studies included only patients at intermediate‐2/high International Prognostic Score System risk, safety and efficacy data in intermediate‐1 patients are limited. We report on 70 intermediate‐1 patients treated with ruxolitinib according to standard clinical practice that were evaluated for response using the 2013 IWG‐MRT criteria. At 6 months, rates of spleen and symptoms response were 54.7% and 80% in 64 and 65 evaluable patients, respectively. At 3 months, ruxolitinib‐induced grade 3 anemia and thrombocytopenia occurred in 40.6% and 2.9% of evaluable patients, respectively. Notably, 11 (15.9%) patients experienced at least one infectious event ≥grade 2. Most (82.6%) patients were still on therapy after a median follow‐up of 27 months. These data support the need for standardized guidelines that may guide the decision to initiate ruxolitinib therapy in this risk category, balancing benefit expectations and potential adverse effects.     

Identification of miRNA profiling in prediction of tumor recurrence and progress and bioinformatics analysis for patients with primary esophageal cancer: Study based on TCGA database

Object

This study focused on the identification of prognostic miRNAs for the prediction of tumor recurrence and progress in esophageal cancer.

Neutralizing antibody responses to subtype B and C adjuvanted HIV envelope protein vaccination in rabbits

Improving the potency, breadth, and durability of neutralizing antibody responses to HIV are major challenges for HIV vaccine development. To address these challenges, the studies described evaluate in rabbits the titers, breadth, and epitope specificities of antibody responses elicited by HIV envelope subunit vaccines adjuvanted with MF59 with or without CpG oligodeoxynucleotide (ODN). Animals were immunized with trimeric o-gp140ΔV2 derived from subtype B HIV-1_SF162 or subtype C HIV-1_TV1, or proteins from both strains. Immunization with SF162 or TV1 with MF59/CpG elicited higher titers of binding and neutralizing antibodies to SF162 than monovalent immunization with MF59 alone (P < 0.01). Bivalent immunization increased binding and neutralizing antibody titers over single envelope immunization in MF59 (P < 0.01). Bivalent immunization also improved neutralization breadth. Epitope mapping indicated neutralizing activity in rabbits was directed to V3 and V4. Overall, our data suggests that a multivalent vaccination approach with MF59 and CpG can enhance humoral responses to HIV-1.     

Human T-lymphotropic virus type-1 (HTLV-1) in Israeli patients and their family relatives and its transmission to rats

We tested the possibility that lymphocytes, sera and saliva, obtained directly from healthy human T-lymphotropic virus type 1 (HTLV-1) carriers and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of Iranian Mashhadi origin, as well as lymphocytes from patients with mycosis fungoides (MF) and their family relatives (MFR), may be infective. Peripheral blood mononuclear cells (PBMC), sera, PBMC cultured with phytohaemagglutinin A and phorbol myristate acetate, cell-free supernatant from these cultures, saliva cells and cell-free saliva were injected into adult WKA (n=107) and F344 (n=47) female rats. The appearance of anti-HTLV-1 antibodies in the rat sera was tested by particle agglutination assay and ELISA, and positive results were confirmed by western blot assay. Higher titers (1:1024) of anti-HTLV-1 antibodies were found in the F344 rats as compared to the WKA rats (1:256). The PA agglutination test was the most sensitive for the detection of HTLV-1 antibody. The HTLV-1 provirus was detected in both strains of rats infected with body fluids and cells from the Iranian Mashhadi Jews, in various organs (PBMC, spleen, thymus, salivary glands, spinal cord, kidney and brain) by nested PCR. However, the HTLV-1 provirus was not detected in 100% of the rats. The negative rats were only immunized and not infected. The spleen, thymus, spinal cord and salivary glands of the seropositive rats were found to be infectious and to transmit the HTLV-1 to healthy rats. F344 rats infected with PBMC cultures obtained from HTLV-1 antibody positive MF patients and their MFR who were only 20% positive showed anti-HTLV-1 antibodies, but only in 20% of rats without showing the HTLV-1 provirus; these rats were probably not infected but only immunized. This is one of the few studies on the transmission of HTLV-1 to rats by inoculation with human infectious fluids or cells from HTLV-1 infected healthy carriers (42%), HAM/TSP patients of Iranian Mashhadi origin (58%) as well as lymphocyte cultures obtained from HTLV-1 antibody positive MF and MFR of nonIranian origin.     

银屑病停用TNF-α拮抗剂后诱发红皮病一例

患者,男,31岁。全身鳞屑性斑块5年,接受TNF-α拮抗剂治疗8个月后皮疹复发,停药2周后全身泛发红斑、丘疹、鳞屑,伴发热。诊断为红皮病型银屑病,给予IL-17A拮抗剂1周后皮损得到控制。     

Utility of multifrequency bioelectrical impedance compared with dual-energy x-ray absorptiometry for assessment of total and regional body composition varies between men and women

Multifrequency bioelectrical impedance analysis of body composition may be an appropriate alternative to dual-energy x-ray absorptiometry. We hypothesized that there would be no significant differences between dual-energy x-ray absorptiometry and either the Biospace (Los Angeles, CA, USA) InBody 520 or 720 multifrequency bioelectrical impedance analysis devices for total lean body mass (LBM), appendicular lean mass (ALM), trunk lean mass (TM), and total fat mass (FM) in 25 men and 25 women (including lean, healthy, and obese individuals according to body mass index), age 18 to 49 years, weight of 73.6 ± 15.4 kg. Both devices overestimated LBM in women (~ 2.5 kg, P < .001) and underestimated ALM in men (~ 3.0 kg, P < .05) and women (~ 1.0 kg, P < .05). The 720 overestimated FM in men (1.6 kg, P < .05) and underestimated TM in women (0.6 kg, P ≤ .05). Regression analyses in men revealed R² (0.87-0.91), standard error of the estimate (SEE; 2.3-2.8 kg), and limits of agreement (LOAs; 4.5-5.7 kg) for LBM; R² (0.62-0.87), SEE (1.5-2.6 kg), and LOA (3.2-6.0 kg) for ALM; R² (0.52-0.71), SEE (2.4-3.0 kg), and LOA (4.6-6.1 kg) for TM; and R² (0.87-0.93), SEE (1.9-2.6 kg), and LOA (5.9-6.2 kg) for FM. Regression analyses in women revealed R² (0.87-0.88), SEE (1.8-1.9 kg), and LOA (4.1-4.2 kg) for LBM; R² (0.78-0.79), SEE (1.4-1.5 kg), and LOA (2.7-2.9 kg) for ALM; R² (0.76-0.77), SEE (1.0 kg), and LOA (2.2-2.3 kg) for TM; and R² (0.95), SEE (2.2 kg), and LOA (4.3-4.4 kg) for FM. The InBody 520 and 720 are valid estimators of LBM and FM in men and of LBM, ALM, and FM in women; the 720 and 520 are valid estimators of TM in men and women, respectively.     

司库奇尤单抗治疗红皮病型银屑病一例并文献复习

报道一例司库奇尤单抗治疗红皮病型银屑病治疗效果并复习相关文献.41岁红皮病型银屑病男性患者,在排除肝炎、结核的基础上,经知情同意后,给予司库奇尤单抗标准方案:0～4周每周皮下注射300 mg,随后每4周注射300 mg.在第4周达到PASI 75,第8周达到PASI 100.随访32周未见明显复发及不良反应.