The influenza hemagglutinin (HA) isolated from avian H7N9 influenza virus strains elicit weak immune responses. This low immunogenicity may be due to a regulatory T cell (Treg)-stimulating epitopes in HA from the H7N9 isolate A/Anhui/1/2013 (Anh/13). In this report, this Treg stimulating sequence was removed from the wild-type (WT) H7 HA amino acid sequence and replaced with a conserved CD4 + T cell stimulating sequences from human seasonal H3N2 strains and designed OPT1 H7 HA. The effectiveness of this optimized H7 HA protein was determined using a humanized mouse (HLA-DR3) expressing the human leukocyte antigen (HLA) DR3 allele. HLA-DR3 mice were pre-immunized by infecting with H3N2 influenza virus, A/Hong Kong/4108/2014 and then vaccinated intramuscularly with either the WT H7 HA from Anh/13 or the OPT1 H7 HA antigen without adjuvant. The OPT1 H7 HA vaccination group elicited higher H7 HA-specific IgG titers that resulted in a lower mortality, weight loss, and lung viral titer following lethal challenge with the H7N9 Anh/13 influenza virus compared to WT-vaccinated mice. Overall, T-cell epitope-engineered vaccines can improve the immunogenicity of H7 HA antigens resulting in enhanced survival and lower morbidity against H7N9 influenza virus challenge.
  The genetic variability and diversity of influenza viruses, and the expansion of their hosts, present a significant threat to human health. The development of a universal influenza vaccine is urgently needed to tackle seasonal epidemics, pandemics, vaccine mismatch, and zoonotic transmissions to humans.
 
  Despite the identification of broadly neutralizing antibodies against influenza viruses, designing a universal influenza vaccine that induces such broadly neutralizing antibodies at protective levels in humans has remained challenging. Besides neutralizing antibodies, multiple correlates of protection have recently emerged as crucially important for eliciting broad protection against diverse influenza viruses. This review discusses the immune responses required for broad protection against influenza viruses, and suggests a paradigm shift from an HA stalk-based approach to other approaches that can induce multiple immunological correlates of protection for the development of a universal influenza vaccine.
 
  To develop a truly universal influenza vaccine, multiple correlates of protection should be considered, including antibody responses and T cell immunity. Balanced induction of neutralizing antibodies, antibody effector functions, and T cell immunity will contribute to the most effective vaccination strategy. Live-attenuated influenza vaccines provide an attractive platform to improve the breadth and potency of vaccines for broader protection.
 To develop a truly universal influenza vaccine, multiple correlates of protection should be considered, including antibody responses and T cell immunity. Balanced induction of neutralizing antibodies, antibody effector functions, and T cell immunity will contribute to the most effective vaccination strategy. Live-attenuated influenza vaccines provide an attractive platform to improve the breadth and potency of vaccines for broader protection.Background No previous studies have determined the incidence of acute kidney injury (AKI) in trauma patients treated with vancomycin + meropenem (VM) versus vancomycin + cefepime (VC). The purpose of this study was to fill this gap. Methods A series of 99 patients admitted to an American College of Surgeons-verified level 1 trauma center over a two-year period who received VC or VM for >48 hours were reviewed retrospectively. Exclusion criteria were existing renal dysfunction or on renal replacement therapy. The primary outcome was AKI as defined by a rise in serum creatinine (SCr) to 1.5 times baseline. Multi-variable analysis was performed to control for factors associated with AKI (age, obesity, gender, length of stay [LOS], nephrotoxic agent(s), and baseline SCr), with significance defined as p  less then  0.05. Results The study population was 50 ± 19 years old, 76% male, with a median LOS of 21 [range 15-39] days, and baseline SCr of 0.9 ± 0.2 mg/dL. Antibiotics, diabetes mellitus, and Injury Severity Score were independent predictors of AKI (odds ratio [OR] 4.4; 95% confidence interval [CI] 1.4-12; OR 9.3; 95% CI 1-27; OR 1.2; 95% CI 1.023-1.985, respectively). The incidence of AKI was higher with VM than VC (10/26 [38%] versus 14/73 [19.1%]; p = 0.049). Conclusions The renal toxicity of vancomycin is potentiated by meropenem relative to cefepime in trauma patients. We recommend caution when initiating vancomycin combination therapy, particularly with meropenem.Long-term inhalation of carbon black nanoparticles (CBNPs) leads to pulmonary inflammatory diseases. Histone deacetylase 6 (HDAC6) has been identified as an important regulator in the development of inflammatory disorders. However, the direct involvement of HDAC6 in CBNPs-induced pulmonary inflammatory responses remains unclear. To explore whether HDAC6 participates in CBNPs-induced pulmonary inflammation, human bronchial epithelial cell line (16HBE cells) was transfected with HDAC6 small interference RNA (siRNA) and then exposed to CBNPs at concentrations of 0, 25, and 50 µg/ml for 24 h. Intracellular HDAC6 and intraflagellar transport protein 88 (IFT88) mRNA and protein were determined by real-time polymerase chain reaction and Western blot, respectively. The secretions of inflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, IL-6, and IL-1β were measured by enzyme-linked immunosorbent assay. CBNPs induced a significant increase in the expressions of IL-8 and IL-6, accompanied by a high level of intracellular HDAC6 mRNA when compared with a blank control group (p 0.05). The HDAC6 mRNA expression was significantly suppressed in HDAC6 siRNA-transfected cells (p less then 0.05). The secretions of IL-8, TNF-α, and IL-6 were significantly less in HDAC6 siRNA-transfected cells than that in normal 16HBE cells with exposure to 25 or 50 µg/ml of CBNPs, but intracellular IFT88 mRNA expression was markedly increased in HDAC6 siRNA-transfected cells when compared with normal 16HBE cells exposed to 50 µg/ml of CBNPs (all p less then 0.05). Downregulation of the HDAC6 gene inhibits CBNPs-induced inflammatory responses in bronchial epithelial cells, partially through regulating IFT88 expression.  https://www.selleckchem.com/products/geneticin-g418-sulfate.html  It is suggested that CBNPs may trigger inflammatory responses in bronchial epithelial cells by an HDAC6/IFT88-dependent pathway.