Probiotics in livestock feed supplements are considered a replacement for antibiotics that enhance gastrointestinal immunity. Although bacterial cell wall components have been proposed to be ...associated with probiotic function, little evidence demonstrates that they are responsible for probiotic functions in livestock. The present study demonstrated that lipoteichoic acid (LTA) of
(Lp.LTA) confers anti-inflammatory responses in porcine intestinal epithelial cell line, IPEC-J2. A synthetic analog of viral double-stranded RNA, poly I:C, dose-dependently induced IL-8 production at the mRNA and protein levels in IPEC-J2 cells. Lp.LTA, but not lipoprotein or peptidoglycan from
, exclusively suppressed poly I:C-induced IL-8 production. Compared with LTAs from other probiotic
strains including
,
, and
GG, Lp.LTA had higher potential to suppress poly I:C-induced IL-8 production. Dealanylated or deacylated Lp.LTA did not suppress poly I:C-induced IL-8 production, suggesting that D-alanine and lipid moieties in the Lp.LTA structure were responsible for the inhibition. Furthermore, Lp.LTA attenuated the phosphorylation of ERK and p38 kinase as well as the activation of NF-κB, resulting in decreased IL-8 production. Taken together, these results suggest that Lp.LTA acts as an effector molecule to inhibit viral pathogen-induced inflammatory responses in porcine intestinal epithelial cells.
Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the ...SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes.
Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT).
Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT
geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization.
ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway.
The trial was registered at ClinicalTrials.gov as # NCT04783311.
The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its ...reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.
•CT-P59 showed the antiviral effect but reduced susceptibility against authentic Gamma, Delta, Epsilon and Kappa variants in cell experiments.•CT-P59 showed neutralizing activity against pseudovirus variants: Gamma, Delta, Epsilon, Kappa, K417T, E484K, N501Y, L452R, T478K and P681H.•Clinically relevant dose of CT-P59 showed in vivo protection against Gamma and Delta variants in hACE2-expressing mice challenge experiments.
To counter the threat of drought, which is expected to increase in the future, we analyzed the combined effects of elevated carbon dioxide (CO
2
) concentration and drought on the photosynthetic ...apparatus and morphological traits in seedlings of yellow poplar (
Liriodendron tulipifera
). The plants were grown for four months in a phytotron under different CO
2
concentrations ambient CO
2
, 430 ppm,
AC
) and elevated CO
2
, 640 ppm,
EC
and water treatment field capacity, FC and 50% of field capacity, FC50. FC50 was sufficient for inducing a reduction in the photosynthetic rate of
L
.
tulipifera
. However, under FC50 combined with
EC
, we observed an increase in photosynthetic rate with increased photopigment content, photochemistry efficiency, and light harvesting ability. Further, decreased specific leaf area and increased wax coverage in
EC
suggested that
EC
contributed to protect chloroplasts and reduce water loss. In conclusion, functional improvements of the photosynthetic apparatus with changes in morphological traits were observed under FC50 combined with
EC
and
EC
ameliorated the adverse effect of FC50 on the seedlings of
L
.
tulipifera
.
Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including ...Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.
Display omitted
•In recent COVID-19 pandemic situation, we established a multicenter COVID-19 efficacy evaluation system.•After receiving 101 applications, the selection committee reviewed and selected 32 final candidates.•Mortality, body weight, viral titer, neutralizing antibody, and histopathology were evaluated in nonclinical efficacy test.•Three vaccines, four antiviral drugs, and two anti-inflammatory drugs showed significant efficacy against COVID-19.
In human intestinal epithelial cells, IFN‐γ induces BAFF expression through the signaling pathway of JAK/STAT and GAS, in the promoter region of the BAFF gene.
BAFF plays an important role in the ...development of B cells. Here, we investigated the effect of IFN‐γ on BAFF expression in human intestinal epithelial cells. IFN‐γ induced soluble and membrane‐bound BAFF production in a dose‐ and time‐dependent manner. IFN‐γ‐induced BAFF release from polarized intestinal epithelial cells was observed in apical and basolateral compartments. JAK I inhibitor suppressed IFN‐γ‐induced BAFF expression. Moreover, IFN‐γ enhanced STAT1 phosphorylation and expression of IRF‐1. Transient transfection and reporter gene assay showed that the BAFF promoter region spanning −750 to −500 bp from the translation initiation site was crucial for IFN‐γ‐induced BAFF expression. Nucleotide sequence analysis revealed a GAS element in the promoter region. ChIP assay confirmed the enhanced binding of phosphorylated STAT1 to the BAFF promoter region at −800 to −601 bp. Furthermore, IFN‐γ enhanced DNA binding to GAS and its transcriptional activation, as determined by the EMSA and reporter gene assay. Collectively, these results suggest that IFN‐γ induces BAFF expression in human intestinal epithelial cells through JAK/STAT signaling pathways that might activate the GAS and IRF‐1‐binding element in the BAFF promoter.
Bacillus ancthracis causes cutaneous, pulmonary, or gastrointestinal forms of anthrax. B. anthracis is a pathogenic bacterium that is potentially to be used in bioterrorism because it can be produced ...in the form of spores. Currently, protective antigen (PA)-based vaccines are being used for the prevention of anthrax, but it is necessary to develop more safe and effective vaccines due to their prolonged immunization schedules and adverse reactions.
We selected the lipoprotein GBAA0190, a potent inducer of host immune response, present in anthrax spores as a novel potential vaccine candidate. Then, we evaluated its immune-stimulating activity in the bone marrow-derived macrophages (BMDMs) using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Protective efficacy of GBAA0190 was evaluated in the guinea pig (GP) model.
The recombinant GBAA0190 (r0190) protein induced the expression of various inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in the BMDMs. These immune responses were mediated through toll-like receptor 1/2 via activation of mitogen-activated protein (MAP) kinase and Nuclear factor-κB (NF-κB) pathways. We demonstrated that not only immunization of r0190 alone, but also combined immunization with r0190 and recombinant PA showed significant protective efficacy against B. anthracis spore challenges in the GP model.
Our results suggest that r0190 may be a potential target for anthrax vaccine.
The threat of drought to trees is predicted to increase due to global warming. In a forest stand, the physiological responses of trees can differ depending on the light conditions. We analyzed ...photosynthetic rate, photopigment, and chlorophyll a fluorescence transient (OJIP test) of
Abies koreana
E.H. Wilson, under different light (full sunlight and 35 and 75% shading) and water conditions (well-watering,
W
; and no-watering,
NW
) to examine the combined effect of light and water. After 21 days of no-watering, we observed decreases in the photosynthetic rate and photopigment contents and quality, impairment of electron transfer from primary to secondary quinone acceptor, inactivation of reaction center, and lower photosynthetic performance index, especially under full sunlight. The time required for recovery after re-watering was also slower under full sunlight. In conclusion, the adverse effects of drought on light absorption and utility of
A
.
koreana
in the photosynthetic process were much greater under high light intensity compared to shading conditions, which alleviated these effects.
Since Bacillus anthracis is a high-risk pathogen and a potential tool for bioterrorism, numerous therapeutic methods including passive immunization have been actively developed. Using a human ...monoclonal antibody phage display library, we screened new therapeutic antibodies for anthrax infection against protective antigen (PA) of B. anthracis. Among 5 selected clones of antibodies based on enzyme-linked immunosorbent assay (ELISA) results, 7B1 showed neutralizing activity to anthrax lethal toxin (LT) by inhibiting binding of the domain 4 of PA (PD4) to its cellular receptors. Through light chain shuffling process, we improved the productivity of 7B1 up to 25 folds. The light chain shuffled 7B1 antibody showed protective activity against LT both in vitro and in vivo. Furthermore, the antibody also conferred protection of mice from 3 × LD50 challenges of fully virulent anthrax spores. Our result expands the possibility of developing a new therapeutic antibody for anthrax cure.
•We screened a novel therapeutic antibody for anthrax using phage display library.•The selected antibody recognizes domain 4 of protective antigen of anthrax toxin.•The selected antibody showed anthrax toxin-neutralizing efficacy in mouse model.
Natural regeneration is an essential component of forest dynamics and the recovery of ecosystem functions. Therefore, understanding regeneration status, and how abiotic and biotic factors affect it, ...is important for ecological studies. This study discovered different regeneration statuses of tropical forests in response to differences in rainfall in Myanmar, and the environmental and overstory factors that had the most influence on understory regeneration. Study sites were set up in regions with 625 to 2035 mm of annual rainfall, and ecological characteristics were measured. According to the results, natural regeneration increased with rainfall, showing a good regeneration status at all sites. Forests within a range of 1411–2035 mm of annual rainfall had a significantly higher density and species diversity at specific natural regeneration stages than those with 625–1029 mm. Not only abiotic but also overstory structure affected the natural regeneration of forests. However, not all factors influenced natural regeneration status. Overstory size distribution parameters did not show a significant influence on natural regeneration. Average annual rainfall (abiotic), as well as ecosystem complexity, density, species richness, and diversity (overstory), were found to be the most influential factors for the density and diversity of natural regeneration. The results of this study will support silviculture and the management of tropical forests.
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