Browsing by Author "Kepler, Thomas B"
Now showing items 1-15 of 15
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Chiropteran types I and II interferon genes inferred from genome sequencing traces by a statistical gene-family assembler.
(BMC Genomics, 2010-07-21)BACKGROUND: The rate of emergence of human pathogens is steadily increasing; most of these novel agents originate in wildlife. Bats, remarkably, are the natural reservoirs of many of the most pathogenic viruses in humans. ... -
Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.
(Nature, 2013-04-25)Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details ... -
Correction: Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.
(PLoS pathogens, 2019-12-02)[This corrects the article DOI: 10.1371/journal.ppat.1008026.]. -
First qualification study of serum biomarkers as indicators of total body burden of osteoarthritis.
(PLoS One, 2010-03-17)BACKGROUND: Osteoarthritis (OA) is a debilitating chronic multijoint disease of global proportions. OA presence and severity is usually documented by x-ray imaging but whole body imaging is impractical due to radiation exposure, ... -
Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.
(Cell host & microbe, 2018-06)HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent ... -
H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.
(PloS one, 2011-01)During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history ... -
Identification and utilization of arbitrary correlations in models of recombination signal sequences.
(Genome Biol, 2002)BACKGROUND: A significant challenge in bioinformatics is to develop methods for detecting and modeling patterns in variable DNA sequence sites, such as protein-binding sites in regulatory DNA. Current approaches sometimes ... -
Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies.
(J Exp Med, 2013-02-11)Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 ... -
Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.
(J Exp Med, 2011-10-24)The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced ... -
Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.
(Nature communications, 2017-11-23)A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms ... -
Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling.
(J Exp Med, 2003-01-20)The recombination signals (RS) that guide V(D)J recombination are phylogenetically conserved but retain a surprising degree of sequence variability, especially in the nonamer and spacer. To characterize RS variability, we ... -
Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.
(Science (New York, N.Y.), 2020-11-19)Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by ... -
Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation.
(Front Immunol, 2014)Affinity maturation of the antibody response is a fundamental process in adaptive immunity during which B-cells activated by infection or vaccination undergo rapid proliferation accompanied by the acquisition of point mutations ... -
The Multiscale Systems Immunology project: software for cell-based immunological simulation.
(Source Code Biol Med, 2008-04-28)BACKGROUND: Computer simulations are of increasing importance in modeling biological phenomena. Their purpose is to predict behavior and guide future experiments. The aim of this project is to model the early immune response ... -
Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design.
(J Virol, 2012-04)Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies ...
