The role of antigen availability during B cell induction and its effect on sustained memory and antibody production after infection and vaccination-lessons learned from the SARS-CoV-2 pandemic

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: [email protected] importance of antibodies, particularly neutralizing antibodies, has been known for decades. When examining the immune responses against a pathogen after a vaccination or infection it is easier to measure the levels of antigen-specific antibodies than the T-cell response, but it does not give the whole picture. The levels of neutralizing antibodies are harder to determine but give a better indication of the quality of the antibody response. The induction of long-lived antibody-secreting plasma cells is crucial for a persistent humoral immune response, which has been shown for example after vaccination with the vaccinia vaccine, where antibody levels have been shown to persist for decades. With the SARS-CoV-2 pandemic ravaging the world for the past years and the monumental effort in designing and releasing novel vaccines against the virus, much effort has been put into analysing the quantity, quality, and persistence of antibody responses.Peer reviewe

TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn's Disease Patients

This work was funded by grants to M.J.W. from the Swedish Cancer Society [CAN2015/463 and CAN 2018/372] and to E.B.L. from the Swedish Government under the ALF agreement [ALFGBG-784211]. Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.BACKGROUND AND AIMS: Uncontrolled activation of intestinal mononuclear phagocytes [MNPs] drives chronic inflammation in inflammatory bowel disease [IBD]. Triggering receptor expressed on myeloid cells 1 [TREM-1] has been implicated in the pathogenesis of IBD. However, the role of TREM-1+ cell subsets in driving IBD pathology and the link with clinical parameters are not understood. We investigated TREM-1 expression in human intestinal MNP subsets and examined blocking TREM-1 as a potential IBD therapy. METHODS: TREM-1 gene expression was analysed in intestinal mucosa, enriched epithelial and lamina propria [LP] layers, and purified cells from controls and IBD patients. TREM-1 protein on immune cells was assessed by flow cytometry and immunofluorescence microscopy. Blood monocyte activation was examined by large-scale gene expression using a TREM-1 agonist or LP conditioned media [LP-CM] from patients in the presence or absence of TREM-1 and tumour necrosis factor [TNF] antagonist antibodies. RESULTS: TREM-1 gene expression increases in intestinal mucosa from IBD patients and correlates with disease score. TREM-1+ cells, which are mainly immature macrophages and CD11b+ granulocytes, increase among LP cells from Crohn's disease patients and their frequency correlates with inflammatory molecules in LP-CM. LP-CM from Crohn's disease patients induces an inflammatory transcriptome in blood monocytes, including increased IL-6 expression, which is reduced by simultaneous blocking of TREM-1 and TNF. CONCLUSIONS: High intestinal TREM-1 expression, reflecting a high frequency of TREM-1+ immature macrophages and TREM-1+CD11b+ granulocytes, is linked to the deleterious inflammatory microenvironment in IBD patients. Therefore, blocking the TREM-1 pathway, especially simultaneously with anti-TNF therapy, has potential as a new IBD therapy.Peer reviewe

Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease

This work was supported in part by The Student Innovation Fund. The funding body had no role in the design of the study, collection, analysis, interpretation of data or writing of the manuscript. Funding Information: We would like to thank Runólfur Pálsson and Elías Eyþórsson for their assistance with the patient demographics. The Department of Clinical Microbiology for their assistance and last but not least the patients. Publisher Copyright: © Copyright © 2021 Brynjolfsson, Sigurgrimsdottir, Einarsdottir, Bjornsdottir, Armannsdottir, Baldvinsdottir, Bjarnason, Gudlaugsson, Gudmundsson, Sigurdardottir, Love, Kristinsson and Ludviksson.A detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys® Anti-SARS-CoV-2 assay on a Roche Cobas® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19.Peer reviewe