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Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants
(2023)bioRxivMost COVID-19 antibody therapies rely on binding the SARS-CoV-2 receptor binding domain (RBD). However, heavily mutated variants such as Omicron and its sublineages, which are characterized by an ever increasing number of mutations in the RBD, have rendered prior antibody therapies ineffective, leaving no clinically approved antibody treatments for SARS-CoV-2. Therefore, the capacity of therapeutic antibody candidates to bind and neutralize ...Working Paper -
B cell clonal expansion is correlated with antigen-specificity in young but not old mice
(2021)bioRxivAging of the humoral immune response has been shown to affect its critical role in defending the host from a variety of pathogens. Technical limitations have nevertheless made it challenging to investigate the relationship between genotype and phenotype of antibody repertoires in the context of aging. We therefore performed single-cell sequencing of over 95,000 B cells to simultaneously investigate B cell receptor (BCR) repertoires and ...Working Paper -
The Physiological Landscape and Specificity of Antibody Repertoires
(2021)bioRxivDiverse antibody repertoires spanning multiple lymphoid organs (e.g., bone marrow, spleen, lymph nodes) form the foundation of protective humoral immunity. Changes in their composition across lymphoid organs are a consequence of B-cell selection and migration events leading to a highly dynamic and unique physiological landscape of antibody repertoires upon antigenic challenge (e.g., vaccination). However, to what extent B cells encoding ...Working Paper -
Clonally expanded virus-specific CD8 T cells acquire diverse transcriptional phenotypes during acute, chronic, and latent infections
(2021)bioRxivCD8+ T cells play a crucial role in the control and resolution of viral infections and can adopt a wide range of phenotypes and effector functions depending on the inflammatory context and the duration and extent of antigen exposure. Similarly, viral infections can exert diverse selective pressures on populations of clonally related T cells. Technical limitations have nevertheless made it challenging to investigate the relationship between ...Working Paper -
Phenotypic determinism and stochasticity in antibody repertoires of clonally expanded plasma cells
(2021)bioRxivThe capacity of humoral B cell-mediated immunity to effectively respond to and protect against pathogenic infections is largely driven by the presence of a diverse repertoire of polyclonal antibodies in the serum, which are produced by plasma cells (PCs).1,2 Recent studies have started to reveal the balance between deterministic mechanisms and stochasticity of antibody repertoires on a genotypic level (i.e., clonal diversity, somatic ...Working Paper