Korean government has selected and stocked five type antigens of two clades as Korean national antigen bank having high possibility of introduction to Korea. We aimed to evaluate the efficacy of the ...clade 2.3.2.1c and 2.3.4.4c H5Nx vaccines from the Korean avian influenza (AI) national antigen bank for emergency preparedness for their potency and protective efficacy against lethal homologous and heterologous viruses in layer and breeder chickens practically. The PD
(dose of vaccine that protects 50% of chickens from viral challenge) of all vaccinated groups was >50, which was satisfied with minimum antigen requirement of OIE, and the PD
levels of the two vaccines differed depending on strain and chicken breed. In homologous challenge, all vaccinated groups exhibited 100% survival with no clinical symptoms and high levels of pre-challenge protective immunity (7.2-8.5 log
), although they did not completely prevent virus shedding. On the other hand, against heterologous virus challenge, vaccinated animals exhibited 62.5-80% survival with lower antibody titers (2.3-3.4 log
) and a longer period of virus shedding (14 days post infection dpi). Our results suggest that the clade 2.3.2.1c and 2.3.4.4c H5Nx vaccines are good candidates for emergency vaccination of commercial chickens and support the idea that close genetic matching between vaccine and challenge virus provides the best protection.
The present study was conducted to monitor sales activity and immunogenicity of commercial H9N2 vaccines produced in Korea from 2007 to 2017. Recorded sales of H9N2 vaccine were around 671 million ...doses, with 10 million doses sold in 2007, rising to a peak of 93 million doses in 2016, with a slight fall in 2017. Multivalent combined vaccines made up around 90% of all vaccine sales, and around 30% of all vaccines were distributed by regional governments for free. The regional vaccination rate was the highest in Gyeonggi and Chungnam, respectively with proportional to the population of layer and breeder chickens. There have been no cases of field infection since 2009. The mean antibody titer was 5.82 log2 across the study period. Our results suggest that continuous genetic monitoring of H9N2 viruses circulating in the field and updating the vaccine seed strain periodically are necessary in order to control H9N2 outbreaks.
The immunogenicity and protective efficacy of inactivated clade 2.3.2.1c (rgKA435) and clade 2.3.4.4c (rgES2) H5Nx vaccines, which are representatives of an avian influenza antigen bank in Korea, ...were examined in mice. Mice were vaccinated twice and then challenged with homologous virus. Hemagglutinin inhibition and serum neutralizing antibody titers in the rgES2-vaccinated group were higher (4.4 ± 1.7 and 10.8 ± 2.3 log2, respectively) than those in the rgKA435-vaccinated group (2.8 ± 1.1 and 2.5 ± 0.9 log2, respectively). rgES2 conferred 100% protection, with no morbidity, no severe body weight loss, and no virus replication in any of the tissues tested. By contrast, 80% of mice in the rgKA435 group survived. One mouse in this group died at 10 dpi. Virus titers in the lung and turbinate were 102.5–3.5 TCID50/0.1 ml at 3–7 dpi and 101.5 TCID50/0.1 ml at 3–5 dpi, respectively. In particular, the viral titer in the turbinate from the rgKA435 group at 3 dpi was significantly lower than that in the equivalent control group (p < 0.05). The data suggest that both of these antigen bank vaccines are promising candidates for further evaluation in humans.
Molecular mechanisms of diabetic kidney disease Reidy, Kimberly; Kang, Hyun Mi; Hostetter, Thomas ...
The Journal of clinical investigation,
06/2014, Letnik:
124, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide and the single strongest predictor of mortality in patients with diabetes. DKD is a prototypical disease of gene and ...environmental interactions. Tight glucose control significantly decreases DKD incidence, indicating that hyperglycemia-induced metabolic alterations, including changes in energy utilization and mitochondrial dysfunction, play critical roles in disease initiation. Blood pressure control, especially with medications that inhibit the angiotensin system, is the only effective way to slow disease progression. While DKD is considered a microvascular complication of diabetes, growing evidence indicates that podocyte loss and epithelial dysfunction play important roles. Inflammation, cell hypertrophy, and dedifferentiation by the activation of classic pathways of regeneration further contribute to disease progression. Concerted clinical and basic research efforts will be needed to understand DKD pathogenesis and to identify novel drug targets.
•Five inactivated vaccines were generated for Korean AI national antigenic bank for HPAI emergency preparedness.•Vaccines provide good protection in SPF chickens against homologous HPAI ...virus.•Vaccines produce high immunity from a single dose with sufficient antigen mass.•Vaccines induce long-lasting antibody responses to prevent mortality and virus shedding.
The occurrence of severe outbreaks of highly pathogenic avian influenza in Korea led to establishment of a national antigen bank for emergency preparedness. Here, we developed five vaccines for this bank (clade 2.3.2.1C, clade 2.3.4.4A, B, C, and D) by reverse genetics, inactivated them with formalin, and evaluated the protective efficacy and potency of serial dilutions against lethal homologous challenge in specific-pathogen-free chickens. After vaccination with one dose, each vaccine resulted in 100% survival, with no clinical symptoms, or lack of detectable virus shedding, and high levels of pre-challenge protective immunity (8.4–10.2 log2). After vaccination with one-tenth of the full dose, protection was similar to that with the full dose. After vaccination with one-hundredth of the initial dose, survival was 20–80%, and all vaccines showed virus shedding. Four vaccines (excluding clade 2.3.2.1C) had satisfactory potency. In antibody-persistence tests, all vaccines maintained long-lasting protective immunity. Our results suggest that inactivated reverse-genetics vaccines genetically matched to outbreak viruses provide adequate protection after a single vaccination.
High pathogenicity H5N1 avian influenza viruses pose a threat to both animal and human health worldwide. In late 2020, outbreaks of H5 high pathogenicity avian influenza viruses belonging to clade ...2.3.4.4b emerged in Europe, following on from outbreaks in East Asia in earlier years. However, very recent studies show that clade 2.3.4.4b H5N1, rather than 2.3.4.4b H5N8, has become predominant in wild birds and has infected poultry in several countries. In this study, we describe isolation of a novel H5N1 virus from a captured mandarin duck in South Korea, and another H5N1 virus from a quail farm. We performed genetic analysis of these two viruses to identify their origin and to determine their relationship with the clade 2.3.4.4b H5N1 viruses currently circulating in Europe. Based on our results, it is presumed that the novel H5N1 virus isolated in Korea originated from an unknown reassortant between clade 2.3.4.4b H5N8 viruses circulating from 2020 and other Eurasian viruses, with additional reassortment of genes and point mutations that discriminate them from the recently reported H5N1 virus in Europe.
Rapid and efficient nucleic acid (NA) extraction and concentration are required for point-of-care analysis in order to prevent an epidemic/pandemic disease outbreak. Typical silica-based NA ...extraction methods have limitations such as being time-consuming, requiring human intervention, and resulting in a low recovery yield. In this study, we have developed a pathogenic DNA extraction device based on electrokinetic separation incorporated with a silicon nitride (SiN
x
) nanofilter, which expedites the DNA extraction procedure with advantages of being convenient, efficient, and inexpensive. This DNA extraction device consists of a computer numerical control (CNC) milled-Teflon gadget with a
cis
-chamber as a cell lysate reservoir and a
trans
-chamber as a elution solution reservoir, with the SiN
x
nanofilter being inserted between the two chambers. The SiN
x
nanofilter was fabricated using a photolithographic method in conjunction with nanoimprinting. Approximately 7.2 million nanopores of 220 nm diameter were located at the center of the nanofilter. When a DC electric field is applied through the nanopores, DNA is transferred from the
cis
-chamber to the
trans
-chamber to isolate the DNA from the cell debris. To demonstrate the DNA extraction performance, we measured the absorbances at 260 and 280 nm and performed a real-time polymerase chain reaction (real-time PCR) using the recovered DNA to verify its feasibility for downstream genetic analysis. Moreover, the DNA extraction device was successfully operated using a 1.5 V alkaline battery, which verifies the portability of the device for point-of-care testing. Such an advanced DNA extraction system can be utilized in various fields including clinical analysis, pathogen detection, forensic analysis, and on-site detection.
A simple electrophoretic DNA extraction device has developed using a nanofilter for rapid and efficient DNA aquisition required for point-of-care analysis in order to prevent an epidemic/pandemic disease outbreak.
Abstract
Virus-like particles (VLPs) are recognized as an alternative vaccine platform that provide effective protection against various highly pathogenic avian influenza viruses (HPAIVs). Here, we ...developed multi-clade VLPs expressing two HAs (a chimera of clade 2.3.2.1c and clade 2.3.4.4c HA) within a single vector. We then compared its protective efficacy with that of a monovalent VLP and evaluated its potency against each homologous strain. Chickens vaccinated with the multi-clade VLP shed less virus and were better protected against challenge than birds receiving monovalent vaccines. Single vaccination with a multi-clade VLP resulted in 100% survival, with no clinical symptoms and high levels of pre-challenge protective immunity (7.6–8.5 log
2
). Moreover, the multi-clade VLP showed high productivity (128–256 HAU) both in the laboratory and on a large scale, making it cheaper than whole inactivated vaccines produced in eggs. However, the PD
50
(protective dose 50%) of the multi-clade VLP against clades 2.3.2.1c and 2.3.4.4c was < 50 PD
50
(28 and 42 PD
50
, respectively), and effective antibody response was maintained for 2–3 months. This multi-clade VLP protects against both clades of HPAI viruses and can be produced in high amounts at low cost. Thus, the vaccine has potential as a pandemic preparedness vaccine.
A reliable method for preparing a conformal amorphous carbon (a‐C) layer with a thickness of 1‐nm‐level, is tested as a possible Cu diffusion barrier layer for next‐generation ultrahigh‐density ...semiconductor device miniaturization. A polystyrene brush of uniform thickness is grafted onto 4‐inch SiO2/Si wafer substrates with “self‐limiting” chemistry favoring such a uniform layer. UV crosslinking and subsequent carbonization transforms this polymer film into an ultrathin a‐C layer without pinholes or hillocks. The uniform coating of nonplanar regions or surfaces is also possible. The Cu diffusion “blocking ability” is evaluated by time‐dependent dielectric breakdown (TDDB) tests using a metal−oxide−semiconductor (MOS) capacitor structure. A 0.82 nm‐thick a‐C barrier gives TDDB lifetimes 3.3× longer than that obtained using the conventional 1.0 nm‐thick TaNx diffusion barrier. In addition, this exceptionally uniform ultrathin polymer and a‐C film layers hold promise for selective ion permeable membranes, electrically and thermally insulating films in electronics, slits of angstrom‐scale thickness, and, when appropriately functionalized, as a robust ultrathin coating with many other potential applications.
A uniform 1‐nm‐level of amorphous carbon (a‐C) layer as a diffusion barrier for Cu interconnects is obtained by the “self‐limited” grafting of a polystyrene brush on oxide dielectric followed by UV crosslinking then carbonization. This approach for generating large area, ultra‐uniform, and ultrathin polymer coatings shows promise for many new research directions and for a broad array of applications.
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