publications of the research group vaccinology and applied
microbiology (VAC)
http://hdl.handle.net/10033/620666
2024-02-02T22:32:21ZPeptidoglycan-treated tumor antigen-pulsed dendritic cells impart complete resistance against tumor rechallenge.
http://hdl.handle.net/10033/623204
Peptidoglycan-treated tumor antigen-pulsed dendritic cells impart complete resistance against tumor rechallenge.
Patidar, A; Selvaraj, S; Chauhan, P; Guzman, C A; Ebensen, T; Sarkar, A; Chattopadhyay, D; Saha, B
2020-06-26T00:00:00ZSymptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.
http://hdl.handle.net/10033/623165
Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.
Langer, Susan; Horn, Johannes; Gottschick, Cornelia; Klee, Bianca; Purschke, Oliver; Caputo, Mahrrouz; Dorendorf, Evelyn; Meyer-Schlinkmann, Kristin Maria; Raupach-Rosin, Heike; Karch, André; Rübsamen, Nicole; Aydogdu, Mustafa; Buhles, Matthias; Dressler, Frank; Eberl, Wolfgang; Koch, Franz Edler von; Frambach, Torsten; Franz, Heiko; Guthmann, Florian; Guzman, Carlos A; Haase, Roland; Hansen, Gesine; Heselich, Valerie; Hübner, Johannes; Koch, Hans Georg; Oberhoff, Carsten; Riese, Peggy; Schild, Ralf; Seeger, Sven; Tchirikov, Michael; Trittel, Stephanie; von Kaisenberg, Constantin; Mikolajczyk, Rafael
Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.
2022-01-05T00:00:00ZItaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.
http://hdl.handle.net/10033/623164
Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.
Sohail, Aaqib; Iqbal, Azeem A; Sahini, Nishika; Chen, Fangfang; Tantawy, Mohamed; Waqas, Fakhar; Winterhoff, Moritz; Ebensen, Thomas; Schultz, Kristin; Geffers, Robert; Schughart, Klaus; Preusse, Matthias; Shehata, Mahmoud; Bähre, Heike; Pils, Marina C; Guzman, Carlos A; Mostafa, Ahmed; Pleschka, Stephan; Falk, Christine; Michelucci, Alessandro; Pessler, Frank
Excessive inflammation is a major cause of morbidity and mortality in many viral infections including influenza. Therefore, there is a need for therapeutic interventions that dampen and redirect inflammatory responses and, ideally, exert antiviral effects. Itaconate is an immunomodulatory metabolite which also reprograms cell metabolism and inflammatory responses when applied exogenously. We evaluated effects of endogenous itaconate and exogenous application of itaconate and its variants dimethyl- and 4-octyl-itaconate (DI, 4OI) on host responses to influenza A virus (IAV). Infection induced expression of ACOD1, the enzyme catalyzing itaconate synthesis, in monocytes and macrophages, which correlated with viral replication and was abrogated by DI and 4OI treatment. In IAV-infected mice, pulmonary inflammation and weight loss were greater in Acod1-/- than in wild-type mice, and DI treatment reduced pulmonary inflammation and mortality. The compounds reversed infection-triggered interferon responses and modulated inflammation in human cells supporting non-productive and productive infection, in peripheral blood mononuclear cells, and in human lung tissue. Itaconates reduced ROS levels and STAT1 phosphorylation, whereas AKT phosphorylation was reduced by 4OI and DI but increased by itaconate. Single-cell RNA sequencing identified monocytes as the main target of infection and the exclusive source of ACOD1 mRNA in peripheral blood. DI treatment silenced IFN-responses predominantly in monocytes, but also in lymphocytes and natural killer cells. Ectopic synthesis of itaconate in A549 cells, which do not physiologically express ACOD1, reduced infection-driven inflammation, and DI reduced IAV- and IFNγ-induced CXCL10 expression in murine macrophages independent of the presence of endogenous ACOD1. The compounds differed greatly in their effects on cellular gene homeostasis and released cytokines/chemokines, but all three markedly reduced release of the pro-inflammatory chemokines CXCL10 (IP-10) and CCL2 (MCP-1). Viral replication did not increase under treatment despite the dramatically repressed IFN responses. In fact, 4OI strongly inhibited viral transcription in peripheral blood mononuclear cells, and the compounds reduced viral titers (4OI>Ita>DI) in A549 cells whereas viral transcription was unaffected. Taken together, these results reveal itaconates as immunomodulatory and antiviral interventions for influenza virus infection.
2022-01-13T00:00:00ZA SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations.
http://hdl.handle.net/10033/623030
A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations.
Bertoglio, Federico; Fühner, Viola; Ruschig, Maximilian; Heine, Philip Alexander; Abassi, Leila; Klünemann, Thomas; Rand, Ulfert; Meier, Doris; Langreder, Nora; Steinke, Stephan; Ballmann, Rico; Schneider, Kai-Thomas; Roth, Kristian Daniel Ralph; Kuhn, Philipp; Riese, Peggy; Schäckermann, Dorina; Korn, Janin; Koch, Allan; Chaudhry, M Zeeshan; Eschke, Kathrin; Kim, Yeonsu; Zock-Emmenthal, Susanne; Becker, Marlies; Scholz, Margitta; Moreira, Gustavo Marçal Schmidt Garcia; Wenzel, Esther Veronika; Russo, Giulio; Garritsen, Hendrikus S P; Casu, Sebastian; Gerstner, Andreas; Roth, Günter; Adler, Julia; Trimpert, Jakob; Hermann, Andreas; Schirrmann, Thomas; Dübel, Stefan; Frenzel, André; van den Heuvel, Joop; Čičin-Šain, Luka; Schubert, Maren; Hust, Michael
The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.
2021-07-07T00:00:00Z