A5103264897- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- COVID-19 Impact on Reproduction
- Respiratory viral infections research
- Chronic Lymphocytic Leukemia Research
- Glycosylation and Glycoproteins Research
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- Blood groups and transfusion
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- SARS-CoV-2 detection and testing
- Advanced biosensing and bioanalysis techniques
- HIV-related health complications and treatments
Fred Hutch Cancer Center
2020-2025
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2023-2025
Cancer Research Center
2023
A major goal of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efforts is to elicit antibody responses that confer protection. Mapping the epitope targets SARS-CoV-2 response critical for design, diagnostics, and development therapeutics. Here, we develop a pan-coronavirus phage display library map binding sites at high resolution within complete viral proteomes all known human-infecting coronaviruses in patients with mild or moderate/severe disease 2019...
The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in receptor binding domain of S1 subunit spike glycoprotein have led to considerable escape antibody responses, reducing efficacy vaccines monoclonal (mAb) therapies. Therefore, there is need interrogate more constrained regions spike, such as S2 subdomain. Here, we present collection...
Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, understanding selective forces guiding maturation, and underlying biochemical process. High throughput data offers potential to develop fit on relevant sets. In this paper we model using modern frameworks. We motivated by recent work suggesting importance a wider context SHM, however, assigning an independent rate each k-mer...
Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, understanding selective forces guiding maturation, and underlying biochemical process. High throughput data offers potential to develop fit on relevant sets. In this paper we model using modern frameworks. We motivated by recent work suggesting importance a wider context SHM, however, assigning an independent rate each k-mer...
Macaques are a commonly used model for studying immunity to human viruses, including studies of SARS-CoV-2 infection and vaccination. However, it is unknown whether macaque antibody responses resemble the response in humans. To answer this question, we employed phage-based deep mutational scanning approach (Phage-DMS) compare which linear epitopes targeted on Spike protein convalescent humans, (re-infected) rhesus macaques, mRNA-vaccinated repRNA-vaccinated pigtail macaques. We also...
Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, which is the betacoronavirus causes COVID-19, but whether these responses influence SARS-CoV-2 infection still under investigation and particularly understudied in infants. In this study, we measured eHCoV SARS-CoV-1 IgG antibody titers before after seroconversion a cohort of Kenyan women their binding were not consistently associated infants or mothers; however, observed very modest...
We present the phippery software suite for analyzing data from phage display methods that use immunoprecipitation and deep sequencing to capture antibody binding peptides, often referred as PhIP-Seq. It has three main components can be used separately or in conjunction: (i) a Nextflow pipeline, phip-flow, process raw into compact, multidimensional dataset format allows end-to-end automation of reproducible workflows. (ii) Python API, phippery, which provides interfaces tasks such count...
Abstract Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, understanding selective forces guiding maturation, and underlying biochemical process. High throughput data offers potential to develop fit on relevant sets. In this paper we model using modern frameworks. We motivated by recent work suggesting importance a wider context SHM, however, assigning an independent rate each...
Abstract Studying vertical human immunodeficiency virus (HIV) transmission enables the impact of passively transferred antibodies on HIV and pathogenesis to be examined. Using phage display envelope peptides peptide enzyme-linked immunosorbent assay (ELISA), we found that, in infants who acquired HIV, passive antibody responses constant region 5 (C5) were associated with improved survival 2 cohorts. In a combined analysis, C5 ELISA activity was correlated directly estimated infection time...
Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, the betacoronavirus causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and particularly understudied in infants. In this study, we measured eHCoV SARS-CoV-1 IgG antibody titers before after seroconversion a cohort of Kenyan women their binding were not consistently associated infants or mothers, though observed very modest association...
The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in receptor binding domain of S1 subunit spike glycoprotein have led to considerable escape antibody responses, reducing efficacy vaccines monoclonal (mAb) therapies. Therefore, there is need interrogate more constrained regions Spike, such as S2 subdomain. Here, we describe collection...
Abstract Antibodies and B-cell receptors (BCRs) are produced by B cells, built of a heavy chain light chain. Although each cell could express two different chains four chains, usually only unique pair is expressed—a phenomenon known as allelic exclusion . However, small fraction naive-B cells violate expressing productive one which has impaired function; this been called inclusion We demonstrate that these can be used to learn constraints on antibody sequence. Using large-scale single-cell...
Human natural history and vaccine studies support a protective role of antibody-dependent cellular cytotoxicity (ADCC) activity against many infectious diseases. One setting where this has consistently been observed is in HIV-1 vertical transmission, passively-acquired ADCC HIV-exposed infants correlated with reduced acquisition risk pathogenesis HIV+ infants. However, the characteristics HIV-specific antibodies comprising maternal plasma response are not well understood. Here, we...
Abstract Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies infants, direct comparisons between infants adults are limited. Here, we characterize binding functionality against Wuhan-Hu-1 (B lineage) strain SARS-CoV-2 convalescent plasma 36 postpartum women 14 their infected with a vaccine-naïve prospective cohort Nairobi, Kenya. We find...
Abstract Macaques are a commonly used model for studying immunity to human viruses, including studies of SARS-CoV-2 infection and vaccination. However, it is unknown whether macaque antibody responses recapitulate, thus appropriately model, the response in humans. To answer this question, we employed phage-based deep mutational scanning approach (Phage- DMS) compare which linear epitopes targeted on Spike protein humans macaques following either vaccination or infection. We also Phage-DMS...
Abstract A major goal of current SARS-CoV-2 vaccine efforts is to elicit antibody responses that confer protection. Mapping the epitope targets response critical for innovative design, diagnostics, and development therapeutics. Here, we developed a phage display library map binding sites at high resolution within complete viral proteomes all human-infecting coronaviruses in patients with mild or moderate/severe COVID-19. The dominant immune were targeted regions spanning Spike protein,...
Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies infants, direct comparisons between infants adults are limited. We characterized binding functionality convalescent plasma postpartum women their infected with SARS-CoV-2 a vaccine-naïve prospective cohort Nairobi, Kenya. Antibody titers against Spike, receptor domain N-terminal domain,...