A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy

Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.     

Comparative toxicity of different chemical and biological insecticides against the scale insect Dactylopius opuntiae and their side effects on the predator Cryptolaemus montrouzieri

The contact toxicity of various chemical and biological pesticides for the first and second instar nymphs and adults of the Opuntia cochineal scale insect Dactylopius opuntiae and the predator ladybird Cryptolaemus montrouzieri was determined under Morocco semi field conditions. d-limonene (60?g/l) at 100 and 150?cc/hl, mineral oil (780?g/l) at 2400?cc/hl and malathion (500?g/l) at 300?cc/hl caused the highest mortality (99–100%) among first instar nymphs of D. opuntiae 24?h after treatment. d-limonene (60?g/l) at 150?cc/hl caused greatest mortality (99%) in second instar nymphs. The highest mortality (99%) among adult female D. opuntiae was observed 120?h after treatment with d-limonene (60?g/l) at 150?cc/hl and mineral oil (780?g/l) at 2400?cc/hl. For the predator C. montrouzieri the highest mortality (92–97%) among adults 24?h after treatment was caused by malathion (500?g/l) at 100, 200 and 300?cc/hl and alpha-cypermethrin (100?g/l) at 75, 150 and 225?cc/hl. The most harmful pesticides to C. montrouzieri larvae 24?h after treatment were malathion and alpha-cypermethrin with mortality rates of 89–95%. Mortality in larvae ranged from 87 to 100% 120?h after treatment with chlorpyriphos-methyl (480?g/l) at 75, 150 and 225?cc/hl and spinosad (480?g/l) at 100, 200 and 300?cc/hl. d-limonene (60?g/l) at 50?cc/hl and mineral oil (780?g/l) at 1000?cc/hl had the least impact on C. montrouzieri adults and larvae, causing mortality of 11 and 15%, respectively, 120?h after treatment. d-limonene (60?g/l) and mineral oil (780?g/l) may therefore be viable alternatives to others high-risk chemical pesticides. These two biological insecticides are effective in controlling the Opuntia cochineal scale insect but have little adverse impact on the predator C. montrouzieri.     

Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands: A prospective cohort study

BackgroundEmerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants.Methods and findingsIn a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231–556] and 214 [95% CI 153–299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11–30] and 14 [95% CI 8–25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02–0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data.ConclusionsOverall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination.

Marit J. van Gils and colleagues investigate antibody responses against diverse emerging SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands.     

Genetic Variation in the Interleukin-28B Gene Is Associated with Spontaneous Clearance and Progression of Hepatitis C Virus in Moroccan Patients

Background

Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population.

Methods

We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5′ allelic discrimination assay.

Results

The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99–11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19–66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99–3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08–8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40–3.93; p = 0.0100).

Conclusions

In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection.     

Modeling of polyphenols extraction from pomegranate by-product using rotatable central composite design of experiments

There is a growing request to find an effective method of polyphenols extraction from agro-industry by-product as pomegranate. In this study, response surface methodology (RSM) was used to explore the effect of three factors on ultrasonic assisted extraction (UAE) of total polyphenols (TP), total flavonoids (TF) and condensed tannins (CT) from pomegranate peels. The optimal conditions were determined for each phenolic compound using regression model equations and 3-D plots. The high TP, TF and CT content were obtained with, respectively, liquid/solid ratio of 20.00, 9.77, 9.77, extraction time of 36.38, 41.82, 30.39 min and 36.00, 83.64, 59.26% of ethanol percentage. In fact, liquid/solid ratio of 20, extraction time of 30.94 min and 59.26% of ethanol gives the highest contents of TP, TF and CT simultaneously. The experimental values using optimal conditions agreed with the predicted values. The pomegranate peels extract obtained under optimum conditions have an effective antioxidant activity as determined by ABTS and DPPH assays.     

Disulfide bond formation protects Arabidopsis thaliana glutathione transferase tau 23 from oxidative damage

Background

Glutathione transferases play an important role as detoxifying enzymes. In A. thaliana, elevated levels of reactive oxygen species (ROS), provoked during biotic and abiotic stress, influence the activity of GSTU23. The aim of this study is to determine the impact of oxidative stress on the function and structure of GSTU23.

Mycoredoxin‐1 is one of the missing links in the oxidative stress defence mechanism of Mycobacteria

To survive hostile conditions, the bacterial pathogen Mycobacterium tuberculosis produces millimolar concentrations of mycothiol as a redox buffer against oxidative stress. The reductases that couple the reducing power of mycothiol to redox active proteins in the cell are not known. We report a novel mycothiol‐dependent reductase (mycoredoxin‐1) with a CGYC catalytic motif. With mycoredoxin‐1 and mycothiol deletion strains of Mycobacterium smegmatis, we show that mycoredoxin‐1 and mycothiol are involved in the protection against oxidative stress. Mycoredoxin‐1 acts as an oxidoreductase exclusively linked to the mycothiol electron transfer pathway and it can reduce S‐mycothiolated mixed disulphides. Moreover, we solved the solution structures of oxidized and reduced mycoredoxin‐1, revealing a thioredoxin fold with a putative mycothiol‐binding site. With HSQC snapshots during electron transport, we visualize the reduction of oxidized mycoredoxin‐1 as a function of time and find that mycoredoxin‐1 gets S‐mycothiolated on its N‐terminal nucleophilic cysteine. Mycoredoxin‐1 has a redox potential of ?218 mV and hydrogen bonding with neighbouring residues lowers the pK_a of its N‐terminal nucleophilic cysteine. Determination of the oxidized and reduced structures of mycoredoxin‐1, better understanding of mycothiol‐dependent reactions in general, will likely give new insights in how M. tuberculosis survives oxidative stress in human macrophages.     

T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy

HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations.     

Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-κB, p38MAPK and Akt inhibition

Chronic inflammation is a hallmark of several pathologies, such as rheumatoid arthritis, gastritis, inflammatory bowel disease, atherosclerosis and cancer. A wide range of anti-inflammatory chemicals have been used to treat such diseases while presenting high toxicity and numerous side effects. Here, we report the anti-inflammatory effect of a non-toxic, cost-effective natural agent, polyphenolic extract from the Tunisian quince Cydonia oblonga Miller. Lipopolysaccharide (LPS) treatment of human THP-1-derived macrophages induced the secretion of high levels of the pro-inflammatory cytokine TNF-α and the chemokine IL-8, which was inhibited by quince peel polyphenolic extract in a dose-dependent manner. Concomitantly, quince polyphenols enhanced the level of the anti-inflammatory cytokine IL-10 secreted by LPS-treated macrophages. We further demonstrated that the unexpected increase in IL-6 secretion that occurred when quince polyphenols were associated with LPS treatment was partially responsible for the polyphenols-mediated inhibition of TNF-α secretion. Biochemical analysis showed that quince polyphenols extract inhibited the LPS-mediated activation of three major cellular pro-inflammatory effectors, nuclear factor-kappa B (NF-κB), p38MAPK and Akt. Overall, our data indicate that quince peel polyphenolic extract induces a potent anti-inflammatory effect that may prove useful for the treatment of inflammatory diseases and that a quince-rich regimen may help to prevent and improve the treatment of such diseases.