B-Cell Program PIs
The ten investigators funded for the new B-cell program are the following:
Dennis R. Burton, Ph.D., professor, The Scripps Research Institute
Probing the Germlines of Broadly Neutralizing Anti-HIV Antibodies in Knockin Mice (U01)
Dr. Burton and colleagues will develop mouse strains that produce B cells with germline versions of broadly neutralizing antibodies and will follow responses to test immunogens. This approach allows the rapid screening of vaccine candidates for their ability to elicit neutralizing antibodies in a context where appropriate precursors are abundant.
James E. Crowe, Jr., M.D., professor, Vanderbilt University School of Medicine
Clonal Analysis of the Human B-Cell Response to HIV (U01)
A consortium led by Dr. Crowe will determine whether, compared to rapid progressors, people who control HIV have a B-cell repertoire that more broadly uses VH segments and whether they have more somatic hypermutation that results in higher affinity antibodies with more neutralizing potency. They will study the molecular genetics of antibody genes from HIV-specific cells from these two groups and repertoire changes that may effect the neutralizing function.
Donald N. Forthal, M.D. chief of infectious diseases, University of California, Irvine
Protective Immunity Against HIV: The Role of IgG Subclass and Glycosylation (R21)
Dr. Forthal and coworkers will investigate IgG subclass and Fc glycosylation, two properties of an antibody that affect its ability to bind to Fc receptors and inhibit HIV-1. They will study IgG subclass responses from vaccinated patients and determine the association between IgG subclass and Fc glycosylation with anti-HIV-1 activity, with the goal of constructing vaccines that elicit antibodies which optimally engage FcRs.
Maureen M. Goodenow, Ph.D., professor, University of Florida College of Medicine
Characterization of Novel Polyreactive Anti-HIV Antibodies Autoimmunity (R21)
Studying adolescents with autoimmunity with or without HIV infection, Dr. Goodenow’s lab will use high-impact basic immunology studies and innovative methods to search for B-cell types producing broadly reactive neutralizing antibodies with long VH CDR3 and to develop and characterize broadly-neutralizing HIV antibodies by creating a novel phage display library.
Min Lu, Ph.D., associate professor, Weill Cornell Medical College
Presentation of Structural Determinants of the 2F5 Neutralization Epitope (R21)
Dr. Lu and colleagues will use protein chemistry and structural biology approaches to produce stable forms of the tetrameric C43 peptide coiled-coil structure of the gp41 ectodoma to induce broadly reactive neutralizing antibodies. They have recently identified the crystal structure of the C43 peptide containing the 2F5 epitope. His laboratory will also evaluate immune responses elicited by stabilized C43 coiled-coil variants in rabbits and guinea pigs.
Abraham Pinter, Ph.D., member, laboratory head, University of Medicine and Dentistry of New Jersey
Novel Epitopes that Mediate Broad Neutralization of Clade B and C HIV-1 Isolates (U01)
Investigators led by Dr. Pinter have identified patient sera that possess broadly neutralizing activities. They plan to identify epitopes that mediate neutralization and define their structure and distribution by screening patient sera from North American and African cohorts, mapping target epitopes, isolating monoclonal antibodies with broad neutralizing activities from EBV-transformed B-cell cultures, and immunizing rabbits with fusion proteins that express novel targets.
Gerald V. Quinnan Jr., M.D., professor and chair, Uniformed Services University of the Health Sciences
High Potency HIV-1 Broadly Cross-Reactive Neutralization (U01)
These studies explore the reasons for the limited potency of the broadly cross-reactive neutralizing response. Dr. Quinnan’s group has shown that such antibodies are induced in rabbits much more slowly than are non-cross reactive antibodies and with poorer booster effect and potency. The group will elucidate the features of the immunogen and ability of B cells that produce broadly neutralizing antibody to compete with non-neutralizing B cells in germinal centers that may limit the potency of the former.
Ignacio Sanz, M.D., associate professor, University of Rochester School of Medicine and Dentistry
Cellular Origins of HIV Broadly Neutralizing Antibodies (R21)
Capitalizing on their capacity for fine discrimination of B-cell subsets and a powerful screening technology, Dr. Sanz and colleagues will seek to identify the cellular source of broadly neutralizing HIV antibodies and determine if autoreactive B cells are enriched for them. They will isolate B-cell subsets expressing validated surface markers from healthy patients and those with HIV or systemic lupus erythematosis to define promising vaccine targets.
Harry W. Schroeder, Jr., M.D., Ph.D., professor, University of Alabama at Birmingham
Immunoglobulin CDR-H3 and Neutralizing Antibodies to HIV (R21)
Dr. Schroeder’s lab is testing whether enriching for hydrophobic, longer CDR-H3s will force mice to express antibodies enriched for longer and more fat soluble binding structures. They will challenge mutant mice with HIV-1 membrane-proximal external region immunogens, isolate anti-MPER antibodies, test whether these antibodies neutralize HIV, and further correlate structure with function.
Raul M. Torres, Ph.D., assistant professor, University of Colorado at Denver and Health Sciences Center
Marginal Zone B-Cell Response to HIV (R21)
Dr. Torres and coworkers are studying how B-cell populations respond to HIV in naive and immunized mice and will define the HIV envelope-specific antibodies produced by different B cells. They seek to determine whether marginal zone B cells can and do participate in the antibody response to HIV and, if not, whether they can be recruited to do so.
To read the article, see HIV Vaccines and B Cells -- A Promising Pair. |
Subscribe to Alerts
