Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects.

Coxsackievirus B3 regulates T-cell infiltration into the heart by lymphocyte function-associated antigen-1 activation via the cAMP/Rap1 axis.

Coxsackievirus B3 (CVB3) infection can trigger myocarditis and can ultimately lead to dilated cardiomyopathy. It is known that CVB3-induced T-cell infiltration into cardiac tissues is one of the pathological factors causing cardiomyocyte injury by inflammation. However, the underlying mechanism for this remains unclear. We investigated the mechanism of T-cell infiltration by two types of CVB3: the H3 WT strain and the YYFF attenuated strain. T-cell activation was confirmed by changes in the distribution of lymphocyte function-associated antigen-1 (LFA-1). Finally, we identified which viral gene was responsible for LFA-1 activation. CVB3 could infect and activate T-cells in vivo and in vitro, and activated T-cells were detected in CVB3-infected mouse hearts. LFA-1 expressed on the surface of these T-cells had been activated through the cAMP/Rap1 pathway. Recombinant lentiviruses expressing VP2 of CVB3 could also induce LFA-1 activation via an increase in cAMP, whilst VP2 of YYFF did not. These results indicated that CVB3 infection increased cAMP levels and then activated Rap1 in T-cells. In particular, VP2, among the CVB3 proteins, might be critical for this activation. This VP2-cAMP-Rap1-LFA-1 axis could be a potential therapeutic target for treating CVB3-induced myocarditis.

Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine.

The relationship between obesity and vaccine efficacy is a serious issue. Previous studies have shown that vaccine efficacy is lower in the obese than in the non-obese. Here, we examined the influence of obesity on the efficacy of influenza vaccination using high fat diet (HFD) and regular fat diet (RFD) mice that were immunized with 2 types of influenza virus vaccines-cell culture-based vaccines and egg-based vaccines. HFD mice showed lower levels of neutralizing antibody titers as compared with RFD mice. Moreover, HFD mice showed high levels of MCP-1 in serum and adipocytes, and low level of influenza virus-specific effector memory CD8(+) T cells. After challenge with influenza virus, the lungs of HFD mice showed more severe inflammatory responses as compared with the lungs of RFD mice, even after vaccination. Taken together, our data suggested that the inflammatory condition in obesity may contribute to the suppressed efficacy of influenza vaccination.

Immunogenicity and safety of H1N1 influenza hemagglutinin protein expressed in a baculovirus system.

Although most influenza vaccines are produced in eggs, new types of vaccines must be developed. In this study, the immunogenicity and safety of a baculovirus-expressed hemagglutinin (HA) of H1N1 influenza virus (Korea/01/2009; designated "HA-Bac-K") was compared with those of a commercially available baculovirus-expressed HA (designated "HA-Bac-C") and an Escherichia coli-expressed HA (designated "HA-E. Coli-K"). HA-Bac-K succeeded in inducing hemagglutination inhibition and neutralization antibodies in mouse and ferret models. The different immunogenicities observed may be attributable to the different expression systems and purification protocols used. Our work suggests that HA expressed in a baculovirus system is an effective and safe candidate influenza vaccine.

Effect of surface roughness on the subsequent growth of MgO nanowires.

We demonstrated the variation of product morphology by varying the underlying surface characteristics, which were controlled by predeposition annealing. The surface roughness of the underlying In2O3 layer affected the resultant product morphology, indicating that rougher substrate favored the formation of one-dimensional (1D) structures. The obtained MgO nanowires were a single-crystal cubic structure. The PL measurement with a Gaussian fitting exhibited visible light emission bands centered at 2.26 eV and 2.86 eV.

Variation of ZnO shell thickness and its effects on the characteristics of coaxial nanowires.

We have changed the thickness of the ZnO shell layers in SiO(x)/ZnO core-shell nanowires by increasing the atomic layer deposition (ALD) cycle, using diethylzinc (DEZn) and H(2)O as precursors of Zn and O, respectively. The samples were characterized by means of x-ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy, and photoluminescence (PL) spectroscopy. While the thickness of the ZnO shell layers increased almost linearly with increase of the ALD cycle, their tubular morphologies were maintained. The variation in the thickness of the ZnO shell layers was accompanied by changes in the relative intensities of the characteristic ultraviolet (UV) and visible emission bands and by a shift of the UV peak position. On the basis of the observed relationship between the XRD shell grain size and the PL shift, we suggest that the PL shift is attributable to an exciton confinement effect. The findings in this study can be applied to a wide range of materials, and are expected to contribute to the development of potential applications of coaxial nanowires.

Sn-catalyzed growth of MgO nanowires.

We reported the fabrication and characterization of MgO nanowires, which were grown by thermal evaporation of the mixture of MgB2 and Sn powders at 800 degrees C through a vapor-liquid-solid (VLS) process. We characterized as-synthesized MgO nanowires using X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Sn nanoparticles were located at the tips of the nanowires, serving as catalyst for the growth of MgO nanowires. The produced nanowires were of cubic MgO structures with diameters in the range of 10-170 nm. The PL measurement with a Gaussian fitting exhibited visible light emission bands centered at 403, 576, and 720 nm.