Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. ...Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.
South Korea experienced a low prevalence of SARS-CoV-2 until the emergence of the omicron in early 2022, triggering a major community epidemic. To evaluate effectiveness of NVX-CoV2373 and BNT162b2 ...vaccines in Korean population, we conducted an observational study utilizing individual-level case data on laboratory-confirmed SARS-CoV-2 infection, along with vaccination record. A total of 47,078 recipients of NVX-CoV2373 vaccine and 7,561 recipients of BNT162b2 vaccine were eligible for the study. Thirty days post-second doses, COVID-19 rates were 7.9% (595 out of 7561) of NVX-CoV2373 recipients and 8.6 % (647 out of 7561) of BNT162b2 recipients experienced COVID-19. NVX-CoV2373 rates increased to 9.8 % and 11.2 % at 60 and 90 days, while BNT162b2 rates were 10.5 % and 11.3 % at the same intervals. The 22-weeks risk ratios for recipients of the NVX-CoV2373 vaccine as compared with recipients of the BNT162b2 vaccine were 1.11 (95 % CI, 0.99 to 1.25) for laboratory-confirmed SARS-CoV-2 infection. Continued monitoring is essential to evaluate the duration of protection across different vaccine platforms and schedules.
Lactobacillus plantarum DK119 (DK119) isolated from the fermented Korean cabbage food was used as a probiotic to determine its antiviral effects on influenza virus. DK119 intranasal or oral ...administration conferred 100% protection against subsequent lethal infection with influenza A viruses, prevented significant weight loss, and lowered lung viral loads in a mouse model. The antiviral protective efficacy was observed in a dose and route dependent manner of DK119 administration. Mice that were treated with DK119 showed high levels of cytokines IL-12 and IFN-γ in bronchoalveolar lavage fluids, and a low degree of inflammation upon infection with influenza virus. Depletion of alveolar macrophage cells in lungs and bronchoalveolar lavages completely abrogated the DK119-mediated protection. Modulating host innate immunity of dendritic and macrophage cells, and cytokine production pattern appeared to be possible mechanisms by which DK119 exhibited antiviral effects on influenza virus infection. These results indicate that DK119 can be developed as a beneficial antiviral probiotic microorganism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The ectodomain of matrix protein 2 (M2e) of influenza virus is suggested to be a rational target for a universal influenza A vaccine. However, there are some concerns that M2e vaccines might ...not be highly effective in the general population with diverse genetic backgrounds. Here we examined the immunogenicity and protective efficacy of the baculovirus-derived virus-like particles containing multiple M2e (M2eVLP) with AS04 adjuvant in a C57BL/6 mouse strain (H-2b ). M2eVLP vaccine induced significant levels of M2e-specific IgG in C57BL/6 mice after vaccination. Furthermore, M2eVLP adjuvanted with AS04 was more effective than M2eVLP alone in conferring protection as well as in inducing recall humoral and T cell responses specific for M2e after lethal influenza virus challenge. A mechanistic study provides evidence that activation of dendritic cells by the toll-like receptor 4 agonist MPL in the AS04 adjuvant was associated with interferon-γ producing CD4 T cell responses. Our results suggest that AS04 adjuvanted M2eVLP vaccines have the potential to improve cross-protection.
Intramuscular (IM) vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) failed in clinical trials due to vaccine-enhanced respiratory disease. To test the efficacy of skin ...vaccination against respiratory syncytial virus (RSV), we investigated the immunogenicity, efficacy, and inflammatory disease after microneedle (MN) patch delivery of FI-RSV vaccine (FI-RSV MN) to the mouse skin with or without an adjuvant of monophosphoryl lipid A (MPL). Compared to IM vaccination, MN patch delivery of FI-RSV was more effective in clearing lung viral loads and preventing weight loss, and in diminishing inflammation, infiltrating immune cells, and T helper type 2 (Th2) CD4 T cell responses after RSV challenge. With MPL adjuvant, MN patch delivery of FI-RSV significantly increased the immunogenicity and efficacy as well as preventing RSV disease as evidenced by lung viral clearance and avoiding pulmonary histopathology. Improved efficacy and prevention of disease by FI-RSV MN with MPL were correlated with no sign of airway resistance, lower levels of Th2 cytokines and infiltrating innate inflammatory cells, and higher levels of Th1 T cell responses into the lung. This study suggests that MN patch delivery of RSV vaccines to the skin with MPL adjuvant would be a promising vaccination method.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The extracellular domain of M2 (M2e), a small ion channel membrane protein, is well conserved among different human influenza A virus strains. To improve the protective efficacy of M2e vaccines, we ...genetically engineered a tandem repeat of M2e epitope sequences (M2e5x) of human, swine, and avian origin influenza A viruses, which was expressed in a membrane-anchored form and incorporated in virus-like particles (VLPs). The M2e5x protein with the transmembrane domain of hemagglutinin (HA) was effectively incorporated into VLPs at a several 100-fold higher level than that on influenza virions. Intramuscular immunization with M2e5x VLP vaccines was highly effective in inducing M2e-specific antibodies reactive to different influenza viruses, mucosal and systemic immune responses, and cross-protection regardless of influenza virus subtypes in the absence of adjuvant. Importantly, immune sera were found to be sufficient for conferring protection in naive mice, which was long-lived and cross-protective. Thus, molecular designing and presenting M2e immunogens on VLPs provide a promising platform for developing universal influenza vaccines without using adjuvants.
Hemagglutinin (HA)-based current vaccines provide suboptimum cross protection. Influenza A virus contains an ion channel protein M2 conserved extracellular domain (M2e), a target for developing ...universal vaccines. Here we generated reassortant influenza virus rgH3N2 4xM2e virus (HA and NA from A/Switzerland/9715293/2013/(H3N2)) expressing chimeric 4xM2e-HA fusion proteins with 4xM2e epitopes inserted into the H3 HA N-terminus. Recombinant rgH3N2 4xM2e virus was found to retain equivalent growth kinetics as rgH3N2 in egg substrates. Intranasal single inoculation of mice with live rgH3N2 4xM2e virus was effective in priming the induction of M2e specific IgG antibody responses in mucosal and systemic sites as well as T cell responses. The rgH3N2 4xM2e primed mice were protected against a broad range of different influenza A virus subtypes including H1N1, H3N2, H5N1, H7N9, and H9N2. The findings support a new approach to improve the efficacy of current vaccine platforms by recombinant influenza virus inducing immunity to HA and cross protective M2e antigens.
Simple, low-cost and scalable patterning methods for Cu nanowire (NW)-based flexible transparent conducting electrodes (FTCEs) are essential for the widespread use of Cu NW FTCEs in numerous flexible ...optoelectronic devices, wearable devices, and electronic skins. In this paper, continuous patterning for Cu NW FTCEs via a combination of selective intense pulsed light (IPL) and roll-to-roll (R2R) wiping process was explored. The development of continuous R2R patterning could be achieved because there was significant difference in adhesion properties between NWs and substrates depending on whether Cu NW coated area was irradiated by IPL or not. Using a custom-built, R2R-based wiping apparatus, it was confirmed that nonirradiated NWs could be clearly removed out without any damage on irradiated NWs strongly adhered to the substrate, resulting in continuous production of low-cost Cu NW FTCE patterns. In addition, the variations in microscale pattern size by varying IPL process parameters/the mask aperture sizes were investigated, and possible factors affecting on developed pattern size were meticulously examined. Finally, the successful implementation of the patterned Cu NW FTCEs into a phosphorescent organic light-emitting diode (PhOLED) and a flexible transparent conductive heater (TCH) were demonstrated, verifying the applicability of the patterned FTCEs. It is believed that our study is the key step toward realizing the practical use of NW FTCEs in various flexible electronic devices.
The hygroelasticity of oxygen-functionalized graphene (GO)-epoxy nanocomposites is studied. Two different transversely isotropic nanocomposite molecular models are constructed: with uniformly ...distributed and interface-concentrated water molecules, respectively. The stress-strain curves and coefficients of moisture expansion (CMEs) are determined according to moisture content. The degradation of the GO/epoxy interface due to the infiltrated moisture is characterized by interfacial decohesion tests. The micromechanics model is used to derive new closed-form solutions for the effective elastic stiffness and CME of multi-phase composites with interfacial imperfections. Regardless of the moisture distribution, the overall hygroelastic behavior of nanocomposites clearly degrades upon moisture absorption.
Objectives:
Chronic rhinosinusitis (CRS) is a disease with a high prevalence and a high socioeconomic burden. This study aimed to conduct a comprehensive systematic review to update the evidence on ...the use of herbal medicine (HM) for CRS treatment.
Methods:
A total of 14 electronic databases for randomized controlled trials (RCTs) evaluating the effects of HM on the treatment of CRS were searched for articles published before July 2021. The primary outcome was CRS severity post-treatment, measured with the Visual Analogue Scale (VAS) and Total Effective Rate (TER). The risk of bias of the included studies and the quality of evidence of the main findings were assessed using the Cochrane Collaboration’s risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluations tool.
Results:
A total of 80 RCTs were included. Compared to placebo, HM significantly improved CRS severity as measured by TER and VAS. When HM was compared with conventional treatment (CT) as monotherapy or adjuvant therapy, CRS severity measured by TER and VAS, quality of life, Lund-Kennedy endoscopy score, Lund-Mackay computed tomography score, and nasal mucociliary function were significantly improved in the HM group. No serious adverse events associated with HM were reported. The risk of bias was generally unclear, and the quality of evidence ranged from moderate to low.
Conclusion:
This review found some limited clinical evidence that HM or HM combined with CT may be more effective and safer than CT alone in treating CRS. However, the methodological quality of the included studies was generally low, and the quality of the evidence needs to be improved.
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