Florian Klein

University of Cologne

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Co-Authors

Henning Gruell

University of Cologne

106

Clara Lehmann

University Hospital Cologne

Kanika Vanshylla

Janssen (Netherlands)

Michel C. Nussenzweig

Rockefeller University

Gerd Fätkenheuer

University of Cologne

Eva Heger

University of Cologne

Veronica Di Cristanziano

University of Cologne

Lutz Gieselmann

German Center for Infection Research

Christoph Kreer

University Hospital Cologne

Philipp Schommers

University Hospital Cologne

Cooperative Institutions

University of Cologne

502

University Hospital Cologne

461

Heinrich Heine University Düsseldorf

216

German Center for Infection Research

207

Düsseldorf University Hospital

180

Charité - Universitätsmedizin Berlin

169

Institute of Virology of the Slovak Academy of Sciences

132

Heidelberg University

131

Freie Universität Berlin

111

Centrum für Integrierte Onkologie

107

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Olfactory and Gustatory Dysfunction in Coronavirus Disease 2019 (COVID-19)

Clinical Infectious Diseases (2020)

Jan-Christoffer Lüers Alexander C. Rokohl Niklas Loreck Philomena A. Wawer Matos Max Augustin

Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide. Given scarce resources, nonlaboratory diagnostics are crucial. In this cross-sectional study, two-thirds of European patients with confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of these symptoms in early diagnostics.

Coronavirus

2019-20 coronavirus outbreak

10.1093/cid/ciaa525

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Citations (147)

[A method for determining the denominator in general practice--results of a pilot study].

PubMed (1993)

J Szecsenyi N. L. Engelhardt M A Wessel Bär R Florian Klein

In countries with fee for service billing and direct access to specialist care the general practitioner does not know key figures of the population he serves. As the role of general practice in health-service-research, quality assurance activities and the construction of sentinel-networks is becoming more important, valid methods to determine the denominator are needed. Results from five practices suggest that yearly contact groups should be used as a common denominator for general practice in our health care system. For certain groups of patients (e. g. the elderly > 60 yrs.) even quarterly contact groups can give sufficient information to forecast the yearly contact group.

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Citations (2)

Data from CD86+ Antigen-Presenting B Cells Are Increased in Cancer, Localize in Tertiary Lymphoid Structures, and Induce Specific T-cell Responses

Kerstin Wennhold Martin Thelen Jonas Lehmann Simon Schran Ella Preugszat

<div>AbstractThe role of B cells in antitumor immunity and their impact on emerging immunotherapies is increasingly gaining attention. B-cell effector functions include not only secretion of antibodies, but also presentation of antigens to T cells. A physiologic B-cell subset with immunostimulatory properties was described in humans, defined by a high expression of CD86 and downregulation of CD21. We used multicolor flow cytometry and IHC to elucidate abundance and spatial distribution of these antigen-presenting B cells (BAPC) in blood (peripheral blood mononuclear cells, PBMC) and tumor samples of 237 patients with cancer. Antigen-specific T-cell responses to cancer testis antigens were determined using tetramer staining and sorted BAPCs in FluoroSpot assays for selected patients. We found that BAPCs were increased in the tumor microenvironment of 9 of 10 analyzed cancer types with site-specific variation. BAPCs were not increased in renal cell carcinoma, whereas we found a systemic increase with elevated fractions in tumor-infiltrating lymphocytes (TIL) and PBMCs of patients with colorectal cancer and gastroesophageal adenocarcinoma. BAPCs were localized in lymphoid follicles of tertiary lymphoid structures (TLS) and were enriched in tumors with increased numbers of TLSs. BAPCs isolated from tumor-draining lymph nodes of patients with cancer showed increased percentages of tumor antigen–specific B cells and induced responses of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition.</div>

CD86

Tumor Antigen

10.1158/2326-6066.c.6550150.v1

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Citations (0)

Durability of Omicron-neutralizing serum activity following mRNA booster immunization in elderly individuals

medRxiv (Cold Spring Harbor Laboratory) (2022)

Kanika Vanshylla Pinkus Tober‐Lau Henning Gruell Friederike Münn Ralf Eggeling

Abstract Elderly individuals are at high risk for severe COVID-19. Due to modest vaccine responses compared to younger individuals and the time elapsed since prioritized vaccinations, the emerging immune-evasive Omicron variant of SARS-CoV-2 is a particular concern for the elderly. Here we longitudinally determined SARS-CoV-2-neutralizing serum activity against different variants in a cohort of 37 individuals with a median age of 82 years. Participants were followed for 10 months after an initial two-dose BNT162b2 vaccination and up to 4.5 months after a BNT162b2 booster. Detectable Omicron-neutralizing activity was nearly absent after two vaccinations but elicited in 89% of individuals by the booster immunization. Neutralizing titers against the Wu01, Delta, and Omicron variants showed similar post-boost declines and 81% of individuals maintained detectable activity against Omicron. Our study demonstrates the mRNA booster effectiveness in inducing Omicron neutralizing activity and provides critical information on vaccine response durability in the highly vulnerable elderly population.

Booster (rocketry)

Booster dose

10.1101/2022.02.02.22270302

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Citations (1)

Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Caelan E. Radford Philipp Schommers Lutz Gieselmann Katharine H. D. Crawford Bernadeta Dadonaite

Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera known to target the CD4-binding site that neutralize diverse strains of HIV. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one sera targeting two epitopes within the CD4 binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.

Polyclonal antibodies

Epitope mapping

10.1101/2023.03.23.533993

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Lactobacilli Expressing Broadly Neutralizing Nanobodies against HIV-1 as Potential Vectors for HIV-1 Prophylaxis?

Vaccines (2020)

Sarah Kalusche Kanika Vanshylla Franziska Kleipass Henning Gruell Bárbara Müller

In the absence of an active prophylactic vaccine against HIV-1, passively administered, broadly neutralizing antibodies (bnAbs) identified in some chronically infected persons were shown to prevent HIV-1 infection in animal models. However, passive administration of bnAbs may not be suited to prevent sexual HIV-1 transmission in high-risk cohorts, as a continuous high level of active bnAbs may be difficult to achieve at the primary site of sexual transmission, the human vagina with its acidic pH. Therefore, we used Lactobacillus, a natural commensal in the healthy vaginal microbiome, to express bn nanobodies (VHH) against HIV-1 that we reported previously. After demonstrating that recombinant VHHA6 expressed in E. coli was able to protect humanized mice from mucosal infection by HIV-1Bal, we expressed VHHA6 in a soluble or in a cell-wall-anchored form in Lactobacillus rhamnosus DSM14870. This strain is already clinically applied for treatment of bacterial vaginosis. Both forms of VHHA6 neutralized a set of primary epidemiologically relevant HIV-1 strains in vitro. Furthermore, VHHA6 was still active at an acidic pH. Thus, lactobacilli expressing bn VHH potentially represent an attractive vector for the passive immunization of women in cohorts at high risk of HIV-1 transmission.

Active immunization

Sexual transmission

HIV vaccine

Lactobacillus rhamnosus

10.3390/vaccines8040758

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Citations (14)

DXRAM: A Persistent In-Memory Storage for Billions of Small Objects

Florian Klein Michael Schöttner

Large-scale interactive applications and real time data-processing are facing problems with traditional disk-based storage solutions. Because of the often irregular access patterns they must keep almost all data in RAM caches, which need to be manually synchronized with secondary storage and need a lot of time to be re-loaded in case of power outages. In this paper we propose a novel key-value storage keeping all data always in RAM by aggregating resources of potentially many nodes in a data center. We aim at supporting management of billions of small data objects (16-64 byte) like for example needed for storing graphs. A scalable low-overhead meta-data management is realized using a novel range-based ID approach combined with a super-overlay network. Furthermore, we provide persistence by a novel SSD-aware logging approach allowing to recover failed nodes very fast.

Persistent data structure

Auxiliary memory

Overlay network

Data access

10.1109/pdcat.2013.23

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Citations (4)

Safe and effective pool testing for SARS-CoV-2 detection

Journal of Clinical Virology (2021)

Marie Wunsch Dominik Aschemeier Eva Heger Denise Ehrentraut J. Krüger

Pooling

Pipette

10.1016/j.jcv.2021.105018

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Citations (12)

Memory management for billions of small objects in a distributed in-memory storage

Florian Klein Kevin Beineke Michael Schöttner

Large-scale interactive applications and online analytic processing on graphs require fast data access to huge sets of small data objects. DXRAM addresses these challenges by keeping all data always in memory of potentially many nodes aggregated in a data center. In this paper we focus on the efficient memory management and mapping of global IDs to local memory addresses, which is not trivial as each node may store up to one billion of small data objects (16-64 byte) in its local memory. We present an efficient paging-like translation scheme for global IDs and a memory management optimized for many small data objects. The latter includes an efficient incremental defragmentation supporting changing allocation granularities for dynamic data. Our evaluations show that the proposed memory management approach has only a 4-5% overhead compared to state of the art memory allocators with around 20% and the paging-like mapping of globals IDs is faster and more efficient than hash-table based approaches. Furthermore, we compare memory overhead and read performance of DXRAM with RAMCloud.

Paging

Allocator

Auxiliary memory

10.1109/cluster.2014.6968771

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Citations (13)

Table S1 from CD86+ Antigen-Presenting B Cells Are Increased in Cancer, Localize in Tertiary Lymphoid Structures, and Induce Specific T-cell Responses

Kerstin Wennhold Martin Thelen Jonas Lehmann Simon Schran Ella Preugszat

Detailed list of used antibodies

CD86

10.1158/2326-6066.22543129

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Citations (0)