Unexplained longitudinal variability in COVID-19 antibody status by Lateral Flow Immuno-Antibody testing

BackgroundCOVID-19 antibody testing allows population studies to classify participants by previous SARS-CoV-2 infection status. Home lateral flow immune-antibody testing devices offer a very convenient way of doing this, but relatively little is known about how measurement and antibody variability will affect consistency in results over time. We examined consistency by looking at the outcome of two tests three months apart while COVID-19 infection rates were low (summer 2020 in the UK).MethodsThe KCL-Coronavirus Health and Experiences in Colleagues at King’s is an occupational cohort of staff and postgraduate research students. Lateral flow immune-antibody testing kits were sent to participant’s homes in late June 2020 and late September 2020. Participants also completed regular surveys that included asking about COVID-19 symptoms and whether they thought they had been infected.ResultsWe studied 1489 participants returned valid results in both June and September (59% of those sent kits). Lateral flow immune-antibody test was positive for 7.2% in June and 5.9% in September, with 3.9% positive in both. Being more symptomatic or suspecting infection increased the probability of ever being positive. Of those positive in June, 46% (49/107) were negative in September (seroreversion), and this was similar regardless of symptom characteristics, suspicion, and timing of possible infection. A possible outlier was those aged over 55 years, where only 3 of 13 (23%) had seroreversion.DiscussionThese results do not follow the pattern reported from studies specifically designed to monitor seropositivity, which have found greater consistency over time and the influence of presence, timing and severity of symptoms on seroreversion. We suggest several factors that may have contributed to this difference: our low bar in defining initial seropositivity (single test); a non-quantitative test known to have relatively low sensitivity; participants carrying out testing. We would encourage other studies to use these real-world performance characteristics alongside those from laboratory studies to plan and analyse any antibody testing.

Protection induced by a human monoclonal antibody recognizing two different epitopes in a conserved region of streptococcal M proteins

Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococcal infection. The antibodies bind with high affinity to the central region on the surface-bound M protein. One antibody could effectively promote vital immune functions, including phagocytosis and in vivo protection. Remarkably, this antibody only interacts through dual-Fab cis mode, where the Fabs bind to two distinct epitopes in M protein, and with conserved binding across strains. In contrast, another antibody binding to a single epitope in the same region does not bypass the M protein’s virulent effects. A broadly-binding, protective monoclonal antibody is a strong candidate for anti-streptococcal therapy. It also highlights the concept of dual-Fab binding and the accessibility of conserved regions for immune antibody targeting.

Broad specificity of immune helminth scFv library to identify monoclonal antibodies targeting Strongyloides

Antibodies have different chemical properties capable of targeting a diverse nature of antigens. Traditionally, immune antibody libraries are perceived to be disease-specific with a skewed repertoire. The complexity during the generation of a combinatorial antibody library allows for a skewed but diverse repertoire to be generated. Strongyloides stercoralis is a parasite that causes strongyloidiasis, a potentially life-threatening disease with a complex diagnosis that impedes effective control and treatment of the disease. This study describes the isolation of monoclonal antibodies against S. stercoralis NIE recombinant protein using an immune antibody phage display library derived from lymphatic filaria-infected individuals. The isolated antibody clones showed both lambda and kappa light chains gene usage, with diverse amino acid distributions. Structural analysis showed that electropositivity and the interface area could determine the binding affinity of the clones with NIE. The successful identification of S. stercoralis antibodies from the filarial immune library highlights the breadth of antibody gene diversification in an immune antibody library that can be applied for closely related infections.

Changes in Gut Microorganism in Patients with Positive Immune Antibody-Associated Recurrent Abortion

Background. This study is aimed at analyzing the changes in gut microorganism of patients with positive immune antibody-associated recurrent abortion using the 16s rRNA gene sequencing microbiome assay. Methods. The fecal samples from 20 recurrent abortion women with positive immune antibody (positive group) and 20 with negative immune antibody (negative group) were collected. After 16s rRNA gene sequencing, the obtained raw reads underwent quality filtering to obtain the clean tags and then classified into microbial genomes. All effective tags were clustered into operational taxonomic units (OTUs), and the representative sequence was selected for the annotation of taxonomic information, followed by alpha and beta diversity analyses. Results. A total of 43,116 OTUs were obtained in all 40 samples. Bacteroides had the highest relative abundance in the positive group. In the negative group, Bacteroides, Erysipelotrichaceae_UCG-003, Faecalibacterium, and Prevotella_9 had high relative abundance. Alpha diversity analysis results showed that the community richness, community diversity, and phylogenetic diversity in the positive group were higher than that in the negative group. Prevotella_9, Enterococcus, Megasphaera, and Anaerostipes presented significant differences between negative and positive groups. Conclusion. The present study for the first time investigated the gut microbiome involved in positive immune antibody-associated recurrent abortion via the 16s rRNA gene sequencing microbiome assay. The genera that were significantly differential between positive and negative groups may serve as therapeutic targets for positive immune antibody-associated recurrent abortion.