A Comparative Study of Nine SARS-CoV-2 IgG Lateral Flow Assays Using Both Post-Infection and Post-Vaccination Samples

Background: Since the SARS-CoV-2 pandemic, lateral flow assays (LFA) detecting specific antibodies have entered the market in abundance. Despite being CE-IVD-labeled, the antigenic compounds of the assays are often unknown, the performance characteristics provided by the manufacturer are often incomplete, and the samples used to obtain the data are not detailed. Objective: To perform a comparative evaluation of nine lateral flow assays to detect IgG responses against SARS-CoV-2. For the evaluation, a carefully designed serum panel containing post-infection samples and post-vaccination (both mRNA vaccine and inactivated virus vaccine) samples was used. Results: The sensitivity of the assays overall ranged from 9 to 90.3% and the specificity ranged from 94.2 to 100%. Spike protein-containing assays performed generally better than the assays with only nucleocapsid protein. The sensitivity of some assays was higher on post-infection samples, while other assays had a higher sensitivity to post-vaccination samples. Conclusion: A comparative approach in the verification of LFAs with an adequately designed serum panel enabled the identification of the antigens used in the assays. Sensitivities differed between post-infection and post-vaccination samples, depending on the assays used. This demonstrates that the verification of assays must be performed with samples representative of the intended use of the assay

Additional file 1: Supplementary Methods. of Alzheimer disease pathology and the cerebrospinal fluid proteome

Table S1. Demographics and clinical characteristics of subjects removed from the statistical analyses. Table S2. Non-AD versus AD CSF biomarker profile group comparison after selection in all subjects of 26 proteins with LASSO. Table S3. Non-AD versus AD CSF biomarker profile group comparison after selection in subjects with cognitive impairment of 18 proteins with LASSO. Table S4. Correlation of CSF proteins with CSF Aβ1-42. Table S5. Correlation of CSF proteins with CSF tau. Table S6. Correlation of CSF proteins with CSF P-tau181. Table S7. Group comparisons of CSF protein measurements for AD versus non-AD CSF biomarker profiles in all subjects. Table S8. Group comparisons of CSF protein measurements for AD versus non-AD CSF biomarker profiles in subjects with cognitive impairment. Figure S1. Box-plots of CSF proteins (selected with LASSO analyses) for positive and negative CSF profiles of AD pathology in all subjects and subjects with cognitive impairment. Figure S2. Pairwise correlation heatmap of the 26 CSF proteins selected with LASSO for classification of non-AD versus AD CSF biomarker profiles for all subjects. Figure S3. Pairwise correlation heatmap of the 18 CSF proteins selected with LASSO for classification of non-AD versus AD CSF biomarker profiles for subjects with cognitive impairment. Figure S4. Correlations of CSF neurogranin and neuromodulin with CSF tau and P-tau181. Figure S5. Chord diagram of the relationships of 59 CSF proteins with CSF tau, P-tau181, and/or Aβ1-42. Figure S6. Venn diagrams of CSF proteins with significant group comparison differences between AD versus non-AD CSF biomarker profiles and those correlating with CSF Aβ1-42, tau, and P-tau181. Figure S7. Venn diagrams of CSF proteins selected with LASSO to classify non-AD versus AD CSF biomarker profiles and those correlating with CSF Aβ1-42, tau, and P-tau181. (DOCX 2575 kb

De novo protein design enables the precise induction of RSV-neutralizing antibodies

De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a protein design algorithm called TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. In both mice and nonhuman primates, cocktails of three de novo-designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused preexisting antibody responses toward defined neutralization epitopes. Overall, our design approach opens the possibility of targeting specific epitopes for the development of vaccines and therapeutic antibodies and, more generally, will be applicable to the design of de novo proteins displaying complex functional motifs. Copyrigh

Persistent low body weight in humans is associated with higher mitochondrial activity in white adipose tissue

Epub ahead of printBACKGROUND:Constitutional thinness (CT) is a state of low but stable body weight (BMI ≤18 kg/m2). CT subjects have normal-range hormonal profiles and food intake but exhibit resistance to weight gain despite living in the modern world's obesogenic environment.OBJECTIVE:The goal of this study is to identify molecular mechanisms underlying this protective phenotype against weight gain.METHODS:We conducted a clinical overfeeding study on 30 CT subjects and 30 controls (BMI 20-25 kg/m2) matched for age and sex. We performed clinical and integrative molecular and transcriptomic analyses on white adipose and muscle tissues.RESULTS:Our results demonstrate that adipocytes were markedly smaller in CT individuals (mean ± SEM: 2174 ± 142 μm 2) compared with controls (3586 ± 216 μm2) (P 0.75)], with many differentially expressed genes associating with positive metabolic outcomes. Pathway analyses revealed an increase in fatty acid oxidation ( P = 3 × 10-04) but also triglyceride biosynthesis (P = 3.6 × 10-04). No differential response to the overfeeding was observed in the 2 groups.CONCLUSIONS:The distinct molecular signature of the adipose tissue in CT individuals suggests the presence of augm ented futile lipid cycling, rather than mitochondrial uncoupling, as a way to increase energy expenditure in CT individuals. We propose that increased mitochondrial function in adipose tissue is an important mediator in sustaining the low body weight in CT individuals. This knowledge could ultimately allow more targeted approaches for weight management treatment strategies. This trial was registered at clinicaltrials.gov as NCT02004821