An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

<p>Abstract</p> <p>Background</p> <p>A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI) H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP)-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e) of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses.</p> <p>Results</p> <p>Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum) adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses.</p> <p>Conclusions</p> <p>These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.</p

Studies on antiviral effects of siRNAs against H5N1 influenza A virus infection

published_or_final_versionMicrobiologyDoctoralDoctor of Philosoph

Effects of apoptosis protein XIAP inhibitor on the apoptosis and sensitivity of chemotherapy in A549 cell

Background and objective X-linked inhibitor of apoptosis protein (XIAP) is a newly discovered inhibitor of apoptosis protein which prevents apoptosis by inhibiting the activation of caspase. After down-regulating XIAP gene expression in A549 cells, a non-small cell lung cancer (NSCLC) cell lines, we investigated the role of XIAP specific siRNA in apoptosis and chemotherapy sensitivity. Methods The mRNA levels of XIAP gene in A549 cells were assessed using a semi-quantitative reverse transcriptase-PCR (RT-PCR). The expression vector of XIAP small interfering RNA (XIAP siRNA）was constructed and transfected into A549 cells. The transfection was proved effective by the fluorescence microscope. Cell proliferation and cell killing rate after chemotherapeutics treatment were investigated by MTT assay. The rate of apoptosis was detected by flow cytometry assay. Results XIAP siRNA construction was proved successful by enzyme digestion and DNA sequencing. The transfection efficiency in A549 cells from positive transfection group and negative transfection group had no differences. Compared to those in cell from control group, the level of XIAP mRNA expression was significantly decreased, the inhibition activity of Cisplatin was significantly higher in cells from positive transfection group. Proliferation of cells from positive transfection group was significantly inhibited after 24, 48, 72, 96 hours . The rates cell killing and apoptosis in cells from positive transfection group caused by Cisplatin were significantly higher compared to those cells from control group. Conclusion The increased expression of XIAP in NSCLC can inhibit the apoptosis of NSCLC cells and result in NSCLC chemotherapy drug resistance. XIAP siRNA could inhibit the NSCLC cell growth specifically, down-regulation of XIAP gene expression promote apoptosis and increase the chemotherapy sensitivity of NSCLC. XIAP siRNA sequence might become a therapeutic target of NSCLC

A Bayesian displacement field approach to accurate registration of SAR images

Precise registration of synthetic aperture radar (SAR) images is a nontrivial task since a change in radar-acquisition geometry generates image shifts. In existing system, either the transformation functions are oversimplified, or external measures such as digital elevation model and flight track are required to be precise. In this paper, we proposed a generative Bayesian approach to modelling the displacement vectors that map the position of each pixel in the image, thus avoiding degradation of the transformation function. Rather than providing a point estimate for the transformation function, the proposed method yields a full posterior density function of the transformation function. Especially, the Bayesian model learns all the parameters adaptively, and the procedure is fully automatic. The proposed model is comparable in accuracy to state-of-the-art optical flow methods on the challenging Sintel benchmarks, and outperforms currently published SAR image registration methods on some real SAR data with critical scenes

Ferroelectric, ferromagnetic, and dielectric behaviors of (Na0.5Bi0.5)0.98Ce 0.02(Ti0.99Fe0.01)O3-BiFe0.95Mn0.05O3 solid-solution thin film

The (Na0.5Bi0.5)0.98Ce0.02(Ti0.99Fe0.01)O3–BiFe0.95Mn0.05O3 (NBTCeFe–BFOMn) solid-solution thin film was fabricated on LaNiO3/Si substrate by metal organic decomposition. The leakage current density of NBTCeFe–BFOMn film at 400 kV/cm was reduced by approximately two orders of magnitude by reducing the density of oxygen vacancies and forming the defect complexes, compared with Na0.5Bi0.5TiO3 film. Much enhanced ferroelectric and magnetic properties were achieved in NBTCeFe– BFOMn film with a remanent polarization of 32.6 μC/cm2 and a saturated magnetization of 6.2 emu/cm3. The dielectric constant–voltage curve coincides well with the polarization–electric field loop

Self-assembly and release of peste des petits ruminants virus-like particles in an insect cell-baculovirus system and their immunogenicity in mice and goats.

Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small ruminants that has a significant economic impact. For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, VLPs of PPRV were generated in a baculovirus system through simultaneous expression of PPRV matrix (M) protein and hemaglutin in (H) or fusion (F) protein. The released VLPs showed morphology similar to that of the native virus particles. Subcutaneous injection of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG production, increased the levels of virus neutralizing antibodies, and promoted lymphocyte proliferation. Without adjuvants, the immune response induced by the PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV vaccine. Thus, our results demonstrated that VLPs containing PPRV M protein and H or F protein are potential "differentiating infected from vaccinated animals" (DIVA) vaccine candidates for the surveillance and eradication of PPR

Chrysosplenetin inhibits artemisinin efflux in P-gp-over-expressing Caco-2 cells and reverses P-gp/MDR1 mRNA up-regulated expression induced by artemisinin in mouse small intestine

Context: CYP3A4 and P-gp together form a highly efficient barrier for orally absorbed drugs and always share the same substrates. Our previous work revealed that chrysosplenetin (CHR) significantly augmented the rat plasma level and anti-malarial efficacy of artemisinin (ART), partially due to the uncompetitive inhibition effect of CHR on rat CYP3A. But the impact of CHR on P-gp is still unknown. Objective: The present study investigates whether CHR interferes with P-gp-mediated efflux of ART and elucidates the underlying mechanism. Materials and methods: P-gp-over-expressing Caco-2 cells were treated with ART (10 μM) or ART-CHR (1:2, 10:20 μM) in ART bidirectional transport experiment. ART concentration was determined by UHPLC-MS/MS method. Healthy male ICR mice were randomly divided into nine groups (n = 6) including negative control (0.5% CMC-Na solution, 13 mL/kg), ART alone (40 mg/kg), verapamil (positive control, 40 mg/kg), ART-verapamil (1:1, 40:40 mg/kg), CHR alone (80 mg/kg), ART-CHR (1:0.1, 40:4 mg/kg), ART-CHR (1:1, 40:40 mg/kg), ART-CHR (1:2, 40:80 mg/kg) and ART-CHR (1:4, 40:160 mg/kg). The drugs were administrated intragastrically for seven consecutive days. MDR1 and P-gp expression levels in mice small intestine were examined by performing RT-PCR and western blot analysis. ABC coupling ATPase activity was also determined. Results: After combined with CHR (1:2), Papp (AP-BL) and Papp (BL-AP) of ART changed to 4.29 × 10 − 8 (increased 1.79-fold) and 2.85 × 10 − 8 cm/s (decreased 1.24-fold) from 2.40 × 10 − 8 and 3.54 × 10 − 8 cm/s, respectively. Efflux ratio (PBA/PAB) declined 2.21-fold (p < 0.01) versus to ART alone. ART significantly up-regulated both MDR1 mRNA and P-gp levels compared with vehicle, while CHR in combination ratio of 0:1, 0.1:1, 1:1, 2:1 and 4:1 with ART, reversed them to normal levels as well as negative control (p < 0.05). The ATPase activities in ART-CHR 1:4 and CHR alone groups achieved a slight increase (p < 0.05) when compared with ART alone. Discussion and conclusion: These results confirm that CHR inhibited P-gp activity and reverse the up-regulated P-gp and MDR1 levels induced by ART. It suggested that CHR potentially can be used as a P-gp reversal agent to obstruct ART multidrug resistance

Effect of citric-acid-modified chitosan (CAMC) on hydration kinetics of tricalcium silicate (C3S)

Studying the mechanism by which organic admixtures affect the hydration and dissolution of tricalcium silicate (C3S) reveals the effect of organic admixtures on ordinary Portland cement and enables target regulation of cement-based materials. In this study, the effects of citric-acid-modified chitosan (CAMC) on the hydration exotherm, hydration products, and microscopic morphology of C3S were investigated. The interface structures, ion adsorptions, and dissolution properties of CAMC and C3S were analyzed using a molecular dynamics simulation method. The results showed the presence of an attraction between the C3S surface and CAMC due to the existence of Op-Hw, Op-Cas, and Hp-Ow ion pairs. CAMC adsorbed most of the Ca ions released upon dissolution of C3S in the aqueous solution and the resulting pairs exhibited low solubilities. The Ca ions were located on the surfaces of C3S particles, preventing the dissolution of the particles and proving the interference effect of additives on the hydration of the cement silicate phase