Carolin Loos
A5048802653- Gene Regulatory Network Analysis
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Mathematical Biology Tumor Growth
- Single-cell and spatial transcriptomics
- Microbial Metabolic Engineering and Bioproduction
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- SARS-CoV-2 detection and testing
- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- Evolution and Genetic Dynamics
- Receptor Mechanisms and Signaling
- Cell Image Analysis Techniques
- Protein Structure and Dynamics
- Cancer-related gene regulation
- Mosquito-borne diseases and control
- Statistical Methods and Inference
- COVID-19 epidemiological studies
- Complement system in diseases
- Reproductive System and Pregnancy
Ragon Institute of MGH, MIT and Harvard
2020-2024
IIT@MIT
2022-2023
Massachusetts Institute of Technology
2020-2022
Helmholtz Zentrum München
2015-2021
Technical University of Munich
2015-2021
The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has made the development of a vaccine top biomedical priority. In this study, we developed series DNA candidates expressing different forms SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals humoral cellular immune responses, including neutralizing antibody titers at levels comparable to those found convalescent humans macaques infected...
As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures...
Abstract Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death 1–4 . Studies of acute syndrome coronavirus 2 (SARS-CoV-2) infection hamsters 5–7 nonhuman primates 8–10 have generally reported clinical disease, preclinical SARS-CoV-2 vaccine studies demonstrated reduction viral replication the upper lower tracts 11–13 Here we show that high-dose intranasal results including high levels...
Control of the global COVID-19 pandemic will require development and deployment safe effective vaccines.To evaluate immunogenicity Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including kinetics, magnitude, phenotype SARS-CoV-2 spike-specific humoral cellular immune responses.Twenty-five participants were enrolled from July 29, 2020, to August 7, follow-up for this day 71 interim analysis was completed on October 3, 2020; assess durability continue 2 years. This study conducted...
SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal changes the transfer of immunity infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but mechanism underlying this is not established. Here, we used systems serology characterize Fc profile influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across placenta. Influenza-...
BackgroundDevelopment of an effective vaccine against the pathogenic blood-stage infection human malaria has proved challenging, and no candidate affected parasitemia following controlled (CHMI) with Plasmodium falciparum.MethodsWe undertook a phase I/IIa clinical trial in healthy adults United Kingdom RH5.1 recombinant protein vaccine, targeting P. falciparum reticulocyte-binding homolog 5 (RH5), formulated AS01B adjuvant. We assessed safety, immunogenicity, efficacy CHMI. Trial registered...
Abstract Summary PESTO is a widely applicable and highly customizable toolbox for parameter estimation in MathWorks MATLAB. It offers scalable algorithms optimization, uncertainty identifiability analysis, which work very generic manner, treating the objective function as black box. Hence, can be used any problem, user provide deterministic Availability implementation MATLAB toolbox, freely available under BSD license. The source code, along with extensive documentation example downloaded...
Reproducibility and reusability of the results data-based modeling studies are essential. Yet, there has been—so far—no broadly supported format for specification parameter estimation problems in systems biology. Here, we introduce PEtab, a which facilitates using Systems Biology Markup Language (SBML) models set tab-separated value files describing observation model experimental data as well parameters to be estimated. We already implemented PEtab support into eight well-established...
Abstract Motivation Dynamic models are used in systems biology to study and understand cellular processes like gene regulation or signal transduction. Frequently, ordinary differential equation (ODE) model the time dose dependency of abundances molecular compounds as well interactions translocations. A multitude computational approaches, e.g. for parameter estimation uncertainty analysis have been developed within recent years. However, many these approaches lack proper testing application...
Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates mechanisms of remained elusive. Using a systems serology approach to evaluate responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort Nicaragua. Children protected had more anti-envelope (E)...
Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the modification landscape challenged by incorporation new unmodified histones each cycle, principles governing heritability remain unclear. We take a quantitative computational modeling approach describe propagation H3K27 H3K36 methylation states. measure combinatorial patterns mass spectrometry on...
Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, death. However, the role of immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry systems serology to comprehensively profile functions T cells antibodies targeting spike, nucleocapsid, envelope proteins a convalescent cohort COVID-19 subjects who were either hospitalized (n = 20) or 40). To avoid confounding, matched...
Abstract Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have mixed, potentially due to heterogeneous nature CP. Here we perform deep profiling SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, well from hospitalized COVID-19 patients before after administration. The show that, although all recipients exhibit expanded humoral immune...
Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown a delayed fractional (DFx) dosing schedule (0-1-6 month) - using AS01B-adjuvanted RH5.1 malaria antigen substantially improves IgG durability as compared with monthly (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there wider immunological changes DFx were unclear. Here, PfRH5-specific Ig B cell responses analyzed in depth...
The novel coronavirus, SARS-coronavirus (CoV)-2 (SARS-CoV-2), has caused over 17 million infections in just a few months, with disease manifestations ranging from largely asymptomatic infection to critically severe disease. remarkable spread and unpredictable outcomes continue challenge management of this infection. Among the hypotheses explain heterogeneity symptoms is possibility that exposure other coronaviruses (CoVs), or overall higher capability develop immunity against respiratory...
Abstract The mechanisms by which antibodies confer protection vary across vaccines, ranging from simple neutralization to functions requiring innate immune recruitment via Fc-dependent mechanisms. role of adjuvants in shaping the maturation antibody-effector remains under investigated. Using systems serology, we compared licensed vaccines (AS01 B /AS01 E /AS03/AS04/Alum) combined with a model antigen. Antigen-naive adults received two adjuvanted immunizations followed late revaccination...
Dynamics of cellular processes are often studied using mechanistic mathematical models. These models possess unknown parameters which generally estimated from experimental data assuming normally distributed measurement noise. Outlier corruption datasets cannot be avoided. outliers may distort the parameter estimates, resulting in incorrect model predictions. Robust estimation methods required provide reliable estimates presence outliers.In this manuscript, we propose and evaluate for...
Abstract Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response a cohort non-human primates immunized with stable recombinant full-length spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered single or two-dose...