Antibody profiling reveals gender differences in response to SARS-COVID-2 infection

<abstract> <p>The recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an ongoing global COVID-19 pandemic and public health crisis. Detailed study of human immune response to SARS-CoV-2 infection is the important topic for a successful treatment of this disease. Our study was aimed to characterize immune response on the level of antibody profiling in convalescent plasma of patients in Georgia. Antibodies against the following SARS-CoV-2 proteins were studied: nucleocapsid and various regions of spike (S) protein: S1, S2 and receptor binding domain (RBD). Convalescent plasma of patients 6–8 weeks after initial confirmation of SARS-CoV-2 infection were tested. Nearly 80% out of 162 patients studied showed presence of antibodies against nucleocapsid protein. The antibody response to three fragments of S protein was significantly less and varied in the range of 20–30%. Significantly more females as compared to males were producing antibodies against S1 fragment, whereas the difference between genders by the antibodies against nucleocapsid protein and RBD was statistically significant only by one-tailed Fisher exact test. There were no differences between the males and females by antibodies against S2 fragment. Thus, immune response against some viral antigens is stronger in females and we suggest that it could be one of the factors of less female fatality after SARS-CoV-2 infection.</p> </abstract>

Comprehensive antibody profiling of mRNA vaccination in children

With the emergence of SARS-CoV-2 variants, fluctuating mask mandates, and school re-openings, increased infections and disease surged among children recently. Thus, there is an urgent need for COVID-19 vaccines for children of all ages. However, whether young children will respond appropriately to mRNA vaccines remains unclear. Here, we deeply profiled the vaccine-induced humoral immune response in 7-11 year old children receiving the mRNA-1273 vaccine. Vaccinated children induced significantly higher antibody titers and functions compared to naturally infected children. Moreover, we observed comparable SARS-CoV-2 titers and neutralizing activity across variants of concern and superior Fcγ-receptor binding and phagocytic antibodies in children compared to vaccinated adults. Our data indicate that mRNA vaccination elicits robust antibody responses and drives superior antibody functionality in children.

Antibody Subclass and Glycosylation Shift Following Effective TB Treatment

With an estimated 25% of the global population infected with Mycobacterium tuberculosis (Mtb), tuberculosis (TB) remains a leading cause of death by infectious diseases. Humoral immunity following TB treatment is largely uncharacterized, and antibody profiling could provide insights into disease resolution. Here we focused on the distinctive TB-specific serum antibody features in active TB disease (ATB) and compared them with latent TB infection (LTBI) or treated ATB (txATB). As expected, di-galactosylated glycan structures (lacking sialic acid) found on IgG-Fc differentiated LTBI from ATB, but also discriminated txATB from ATB. Moreover, TB-specific IgG4 emerged as a novel antibody feature that correlated with active disease, elevated in ATB, but significantly diminished after therapy. These findings highlight 2 novel TB-specific antibody changes that track with the resolution of TB and may provide key insights to guide TB therapy.

Antibody profiling reveals gender differences in response to SARS-COVID-2 infection

The recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an ongoing global COVID-19 pandemic and public health crisis. Detailed study of human immune response to SARS-COVIS-2 infection is the important topic for a successful treatment of this disease. Our study was aimed to characterize immune response on the level of antibody profiling in convalescent plasma of patients in Georgia. Antibodies against the following SARS-COV-2 proteins were studied: nucleocapsid and various regions of Spike (S) protein: S1, S2 and Receptor binding domain (RBD). Convalescent plasma of patients 6-8 weeks after initial confirmation of SARS-COV-2 infection were tested. Nearly 80% out of 154 patients studied showed presence of antibodies against nucleocapsid protein. The antibody response to three fragments of S protein was significantly less and varied in the range of 20-30%. Significantly more females as compared to males were producing antibodies against S1 fragment, whereas the difference between genders by the antibodies against nucleocapsid protein and RBD was statistically significant only by one-tailed Fisher exact test. There were no differences between the males and females by antibodies against S2 fragment. Thus, immune response against some viral antigens are stronger in females and we suggest that it could be one of the factors of less female fatality after SARS-COVID-2 infection.

Neutralizing IFNL3 Autoantibodies in Severe COVID-19 Identified Using Molecular Indexing of Proteins by Self-Assembly

Unbiased antibody profiling can identify the targets of an immune reaction. A number of likely pathogenic autoreactive antibodies have been associated with life-threatening SARS-CoV-2 infection; yet, many additional autoantibodies likely remain unknown. Here we present Molecular Indexing of Proteins by Self Assembly (MIPSA), a technique that produces ORFeome-scale libraries of proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing. We used MIPSA to profile circulating autoantibodies from 55 patients with severe COVID-19 against 11,076 DNA-barcoded proteins of the human ORFeome library. MIPSA identified previously known autoreactivities, and also detected undescribed neutralizing interferon lambda 3 (IFN-λ3) autoantibodies. At-risk individuals with anti-IFN-λ3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation.One-Sentence SummaryMolecular Indexing of Proteins by Self Assembly (MIPSA) identifies neutralizing IFNL3 autoantibodies in patients with severe COVID-19.Graphical Abstract

Evaluation of a novel extended automated particle-based multi-analyte assay for the detection of autoantibodies in the diagnosis of primary biliary cholangitis

BackgroundAnti-mitochondrial autoantibodies (AMA) detected by indirect immunofluorescence (IIF) on rodent tissues are the diagnostic marker of primary biliary cholangitis (PBC). However, up to 15% of patients with PBC are AMA-negative by IIF. In the effort to close the serological gap and improve the diagnostic sensitivity of PBC testing, recently, novel autoantibodies specific for PBC, such as kelch-like 12 (KLHL12, KLp epitope) and hexokinase 1 (HK1) have been described. In this study, we evaluated the autoantibody profile in a large cohort of PBC patients and in patients with other liver disease, including anti-HK1 and anti-KLp autoantibodies.MethodsSera of 194 PBC patients (126 AMA-IIF-positive and 68 AMA-IIF-negative) and 138 disease controls were tested for a panel of PBC-specific antibodies (MIT3, sp100, gp210, HK1, KLp) using a new automated particle-based multi-analyte technology (PMAT) assay on the Aptiva instrument (Inova).ResultsSelecting a cutoff yielding a specificity of >95% for all the markers, the sensitivity for anti-MIT3, anti-sp100, anti-gp210, anti-HK1 and anti-KLp in the PBC AMA-IIF-negative cohort was 20.6%, 16.2%, 23.5%, 22.0%, 17.6 and 13.2%, respectively. Six out of the 68 (8.8%) AMA-IIF negative sera were positive for anti-HK1 or anti-KLp alone. Using these new markers in addition to anti-MIT3, anti-sp100 and anti-gp210, the overall sensitivity in this cohort of AMA-IIF-negative patients increased from 53% to 61.8%, reducing the serological gap in AMA-negative PBC patients.ConclusionsPBC antibody profiling, made possible by the new Aptiva-PMAT technology, allows recognition of a higher number of AMA-negative PBC patients than conventional immunoassays and may represent a useful tool to evaluate the prognostic significance of autoantibody association in PBC patients.