The humoral immune response after primary immunisation with a SARS-CoV-2 vector vaccine (AstraZeneca AZD1222, ChAdOx1 nCoV-19, Vaxzevria) followed by an mRNA vaccine boost (Pfizer/BioNTech, BNT162b2; ...Moderna, m-1273) was examined and compared with the antibody response after homologous vaccination schemes (AZD1222/AZD1222 or BNT162b2/BNT162b2).
Sera from 59 vaccinees were tested for anti-SARS-CoV-2 immunoglobulin G (IgG) and virus-neutralising antibodies (VNA) with three IgG assays based on (parts of) the SARS-CoV-2 spike (S)-protein as antigen, an IgG immunoblot (additionally contains the SARS-CoV-2 nucleoprotein (NP) as an antigen), a surrogate neutralisation test (sVNT), and a Vero-cell-based virus-neutralisation test (cVNT) with the B.1.1.7 variant of concern (VOC; alpha) as antigen. Investigation was done before and after heterologous (n = 30 and 42) or homologous booster vaccination (AZD1222/AZD1222, n = 8/9; BNT162b2/BNT162b2, n = 8/8). After the second immunisation, a subgroup of 26 age- and gender-matched sera (AZD1222/mRNA, n = 9; AZD1222/AZD1222, n = 9; BNT162b2/BNT162b2, n = 8) was also tested for VNA against VOC B.1.617.2 (delta) in the cVNT. The strength of IgG binding to separate SARS-CoV-2 antigens was measured by avidity.
After the first vaccination, the prevalence of IgG directed against the (trimeric) SARS-CoV-2 S-protein and its receptor binding domain (RBD) varied from 55-95% (AZD1222) to 100% (BNT162b2), depending on the vaccine regimen and the SARS-CoV-2 antigen used. The booster vaccination resulted in 100% seroconversion and the occurrence of highly avid IgG, which is directed against the S-protein subunit 1 and the RBD, as well as VNA against VOC B.1.1.7, while anti-NP IgGs were not detected. The results of the three anti-SARS-CoV-2 IgG tests showed an excellent correlation to the VNA titres against this VOC. The agreement of cVNT and sVNT results was good. However, the sVNT seems to overestimate non- and weak B.1.1.7-neutralising titres. The anti-SARS-CoV-2 IgG concentrations and the B.1.1.7-neutralising titres were significantly higher after heterologous vaccination compared to the homologous AZD1222 scheme. If VOC B.1.617.2 was used as antigen, significantly lower VNA titres were measured in the cVNT, and three (33.3%) vector vaccine recipients had a VNA titre < 1:10.
Heterologous SARS-CoV-2 vaccination leads to a strong antibody response with anti-SARS-CoV-2 IgG concentrations and VNA titres at a level comparable to that of a homologous BNT162b2 vaccination scheme. Irrespective of the chosen immunisation regime, highly avid IgG antibodies can be detected just 2 weeks after the second vaccine dose indicating the development of a robust humoral immunity. The reduction in the VNA titre against VOC B.1.617.2 observed in the subgroup of 26 individuals is remarkable and confirms the immune escape of the delta variant.
By binding to its receptors expressed on intestinal epithelial cells, IL-26 inhibits their proliferation and concomitantly induces the production of pro-inflammatory cytokines TNF-alpha and IL-8 ...11,21. ...increased expression of IL-26 in colonic RORgammat-expressing Th17 cells is correlated with the pathogenesis of Crohn's disease (Fig 2) 21. ...rhIL-26 produced in a prokaryotic expression system was relatively less efficient in killing the bacteria when compared to IL-26 in Th17 cell supernatants. ...the absence of IL-26 in mice has greatly hindered our progress in understanding the antimicrobial functions of IL-26, its regulation, and therapeutic applications for various bacterial diseases.
In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break ...in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors. IL-26 is a member of the IL-10 cytokine family, overexpressed in numerous chronic inflammatory diseases, in which biological activity remains unclear. We demonstrate in this study that IL-26 binds to genomic DNA, mitochondrial DNA, and neutrophil extracellular traps, and shuttles them in the cytosol of human myeloid cells. As a consequence, IL-26 allows extracellular DNA to trigger proinflammatory cytokine secretion by monocytes, in a STING- and inflammasome-dependent manner. Supporting these biological properties, IL-10-based modeling predicts two DNA-binding domains, two amphipathic helices, and an in-plane membrane anchor in IL-26, which are structural features of cationic amphipathic cell-penetrating peptides. In line with these properties, patients with active autoantibody-associated vasculitis, a chronic relapsing autoimmune inflammatory disease associated with extensive cell death, exhibit high levels of both circulating IL-26 and IL-26-DNA complexes. Moreover, in patients with crescentic glomerulonephritis, IL-26 is expressed by renal arterial smooth muscle cells and deposits in necrotizing lesions. Accordingly, human primary smooth cells secrete IL-26 in response to proinflammatory cytokines. In conclusion, IL-26 is a unique cationic protein more similar to a soluble pattern recognition receptor than to conventional cytokines. IL-26 expressed in inflammatory lesions confers proinflammatory properties to DNA released by dying cells, setting up a positive amplification loop between extensive cell death and unabated inflammation.
Herpesvirus saimiri (HVS) is discussed as a possible vector in gene therapy. In order to create a self-repairing HVS vector, the F plasmid vector moiety of the bacterial artificial chromosome (BAC) ...was transposed via Red recombination into the virus genes ORF22 or ORF29b, both important for virus replication. Repetitive sequences were additionally inserted, allowing the removal of the F-derived sequences from the viral DNA genome upon reconstitution in permissive epithelial cells. Moreover, these self-repair-enabled BACs were used to generate deletion variants of the transforming strain C488 in order to minimalize the virus genome. Using the en passant mutagenesis with two subsequent homologous recombination steps, the BAC was seamlessly manipulated. To ensure the replication capacity in permissive monkey cells, replication kinetics for all generated virus variants were documented. HVS variants with increased insert capacity reached the self-repair within two to three passages in permissive epithelial cells. The seamless deletion of ORFs 3/21, 12–14, 16 or 71 did not abolish replication competence. Apoptosis induction did not seem to be altered in human T cells transformed with deletion variants lacking ORF16 or ORF71. These virus variants form an important step towards creating a potential minimal virus vector for gene therapy, for example, in human T cells.
Interleukin 26 (IL-26) is the most recently identified member of the IL-20 cytokine subfamily, and is a novel mediator of inflammation overexpressed in activated or transformed T cells. Novel ...properties have recently been assigned to IL-26, owing to its non-conventional cationic, and amphipathic features. IL-26 binds to DNA released from damaged cells and, as a carrier molecule for extracellular DNA, links DNA to inflammation. This observation suggests that IL-26 may act both as a driver and an effector of inflammation, leading to the establishment of a deleterious amplification loop and, ultimately, sustained inflammation. Thus, IL-26 emerges as an important mediator in local immunity/inflammation. The dysregulated expression and extracellular DNA carrier capacity of IL-26 may have profound consequences for the chronicity of inflammation. IL-26 also exhibits direct antimicrobial properties. This review summarizes recent advances on the biology of IL-26 and discusses its roles as a novel kinocidin.
Zinc oxide (ZnO) tetrapods as microparticles with nanostructured surfaces show peculiar physical properties and anti-infective activities. The aim of this study was to investigate the antibacterial ...and bactericidal properties of ZnO tetrapods in comparison to spherical, unstructured ZnO particles. Additionally, killing rates of either methylene blue-treated or untreated tetrapods and spherical ZnO particles for Gram-negative and Gram-positive bacteria species were determined. ZnO tetrapods showed considerable bactericidal activity against
and
isolates, including multi-resistant strains, while
and
remained unaffected. Almost complete elimination was reached after 24 h for
at 0.5 mg/mL and
at 0.25 mg/mL. Surface modifications of spherical ZnO particles by treatment with methylene blue even improved the antibacterial activity against
. Nanostructured surfaces of ZnO particles provide active and modifiable interfaces for the contact with and killing of bacteria. The application of solid state chemistry, i.e., the direct matter-to-matter interaction between active agent and bacterium, in the form of ZnO tetrapods and non-soluble ZnO particles, can add an additional principle to the spectrum of antibacterial mechanisms, which is, in contrast to soluble antibiotics, depending on the direct local contact with the microorganisms on tissue or material surfaces.
To determine the viral diagnosis and the outcome of eyes with acute retinal necrosis (ARN) treated with intravenous acyclovir and oral prednisolone alone or combined with early vitrectomy and ...intravitreal acyclovir lavage.
Nonrandomized, retrospective, interventional, comparative, consecutive series.
A cohort of 27 human immunodeficiency virus-negative patients with ARN comprising 24 unilateral and 3 bilateral cases.
Vitreous biopsy for viral diagnosis. Twenty eyes were treated with intravenous acyclovir in combination with oral prednisolone (group A). Ten eyes were treated additionally with early vitrectomy, intravitreal acyclovir lavage, laser demarcation of necrotic retinal areas when feasible-with or without scleral buckling, and gas or silicone oil tamponade (group B). Vitrectomy was performed in all cases of secondary rhegmatogenous retinal detachment (RD).
Results of vitreous biopsy, rate of RD, rate of phthisis bulbi, and course of best-corrected visual acuity (BCVA).
Varicella zoster virus (VZV) was detected in 26 eyes, followed by herpes simplex virus (5 eyes), and Epstein-Barr virus (2 eyes, in conjunction with VZV). An RD developed in more eyes in group A (18 of 20 eyes) than in group B (4 of 10 eyes; P = 0.007). In 2 of 20 eyes in group A and in 0 of 10 eyes in group B, phthisis bulbi developed without a significant difference between groups A and B. Mean BCVA (logarithm of the minimum angle of resolution) at first visit was 1.09 (standard deviation SD, 0.83), and mean final BCVA was 1.46 (SD, 0.88) without significant difference between groups A and B.
Varicella zoster virus is the leading cause of ARN. Visual prognosis is guarded. Early vitrectomy with intravitreal acyclovir lavage was associated with a lower incidence of secondary RD; however, it did not improve mean final visual acuity.
Between 2012 and 2015, 495 pooled snout swabs from fattening pigs raised in Schleswig-Holstein, Germany, were screened for the presence of enterovirus G (EV-G) RNA. Nucleic acids were tested in ...diverse reverse transcription polymerase chain reaction assays applying published oligonucleotide primers specific for the viral protein (VP) 1 and 2/4 encoding regions as well as for 3D polymerase. Phylogenetic analyses of VP1 revealed the presence of 12 EV-G types, three of which had highly divergent sequences suggesting putative new types. Co-circulation of EV-G types was observed in several pigsties. Thus, genetic diversity of EV-G was demonstrated in this small geographic area.
The rapid detection of infections caused by the
(SARS-CoV-2) is necessary in the ongoing pandemic. Antigen-specific point-of-care tests (POCT) may be useful for this purpose. Here, such a POCT ...(SARS-CoV-2 NADAL
COVID-19 Ag) was compared to a laboratory-developed triplex real-time polymerase chain reaction (RT-PCR) designed for the detection of viral nucleoprotein gene and two control targets. This RT-PCR served as a reference to investigate POCT sensitivity by re-testing upper respiratory tract (URT) samples (
= 124) exhibiting different SARS-CoV-2 loads in terms of RT-PCR threshold cycle (Ct) values. The optical intensities of the antigen bands were compared to the Ct values of the RT-PCR. The infectivity of various virus loads was estimated by inoculating Vero cells with URT samples (
= 64, Ct 17-34). POCT sensitivity varied from 100% (Ct < 25) to 73.1% (Ct ≤ 30); higher SARS-CoV-2 loads correlated with higher band intensities. All samples with a Ct > 30 were negative; among SARS-CoV-2 free samples (
= 10) no false-positives were detected. A head-to-head comparison with another POCT (Abbott, Panbio™ COVID-19 Ag Rapid Test) yielded similar results. Isolation of SARS-CoV-2 in cell-culture was successful up to a Ct value of 29. The POCT reliably detects high SARS-CoV-2 loads and rapidly identifies infectious individuals.
The cationic proinflammatory cytokine Interleukin 26 (IL-26) shows antibacterial activity and inhibits the replication of cytomegalovirus and hepatitis C virus. This study evaluates the early ...microbicidal activities of IL-26 against major bacterial species including multi-resistant variants and
Candida albicans
. Recombinant IL-26 was bacterially expressed and studied for its microbicidal effects in culture. We show that IL-26 has strong 90% bactericidal activities against
Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus
, and
Acinetobacter baumannii
. Similarly, IL-26 sensitivity was also detectable in vancomycin-resistant Enterococcus species, methicillin-resistant
S. aureus
, and carbapenem-resistant
A. baumannii
clinical isolates. Additionally, a significant, albeit weak fungicidal effect against
Candida albicans
was observed. Activities against
Escherichia coli, Klebsiella pneumoniae
, and
Pseudomonas aeruginosa
were not detectable. The proinflammatory cytokine and kinocidin IL-26 shows strong bactericidal activities against
A. baumannii
and, almost selectively, against Gram-positive bacteria.
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