Institute of Biomedical Sciences
Defining the B-Cell Response to a Stabilized Pre-Fusion Respiratory Syncytial Virus F Subunit Protein Vaccine
Poster Number
17
Document Type
Poster
Status
Graduate Student - Doctoral
Abstract Category
Immunology/Infectious Diseases
Keywords
Vaccine, Respiratory Syncytial Virus, B cell, Clinical Trial
Publication Date
Spring 2018
Abstract
Respiratory syncytial virus (RSV) causes substantial morbidity in children and the elderly, and the only licensed product is a passively administered monoclonal antibody palivizumab. Therefore, a safe and effective RSV vaccine is needed. An effective vaccine will require the induction of neutralizing antibodies, which can be elicited to several antigenic sites present on the pre-fusion (pre-F) and post-fusion (post-F) conformations of the RSV fusion (RSV F) protein. Recently described antigenic sites Ø, V and other surfaces unique to the pre-F conformation are targets for neutralizing antibodies that are more potent than palivizumab, invigorating efforts to create a pre-F vaccine. A stabilized form of the pre-F protein achieved through cysteine substitutions and cavity filling mutations (DS-Cav1) is currently in a phase I clinical trial, where participants receive two immunizations with DS-Cav1 either with or without alum adjuvant in one of three doses (50, 150, or 500 micrograms). We have created tetrameric probes consisting of either the stabilized pre-F or post-F protein bound to a fluorescently labeled streptavidin. These probes bind to the B-cell receptor on the surface of B cells specific for the F protein, and can be used to measure responses elicited by DS-Cav1 vaccination. We have validated the conformation and specificity of the pre-F and post-F probes using antibody binding assays and by staining B cells from antigen-experienced mice. The validated probes, in conjunction with a panel of B cell phenotypic markers, will allow us to interrogate B cell responses longitudinally for antibody repertoire and epitope-specific B cell phenotypes, and compare the responses between participants in the six arms of the clinical trial.
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Open Access
1
Defining the B-Cell Response to a Stabilized Pre-Fusion Respiratory Syncytial Virus F Subunit Protein Vaccine
Respiratory syncytial virus (RSV) causes substantial morbidity in children and the elderly, and the only licensed product is a passively administered monoclonal antibody palivizumab. Therefore, a safe and effective RSV vaccine is needed. An effective vaccine will require the induction of neutralizing antibodies, which can be elicited to several antigenic sites present on the pre-fusion (pre-F) and post-fusion (post-F) conformations of the RSV fusion (RSV F) protein. Recently described antigenic sites Ø, V and other surfaces unique to the pre-F conformation are targets for neutralizing antibodies that are more potent than palivizumab, invigorating efforts to create a pre-F vaccine. A stabilized form of the pre-F protein achieved through cysteine substitutions and cavity filling mutations (DS-Cav1) is currently in a phase I clinical trial, where participants receive two immunizations with DS-Cav1 either with or without alum adjuvant in one of three doses (50, 150, or 500 micrograms). We have created tetrameric probes consisting of either the stabilized pre-F or post-F protein bound to a fluorescently labeled streptavidin. These probes bind to the B-cell receptor on the surface of B cells specific for the F protein, and can be used to measure responses elicited by DS-Cav1 vaccination. We have validated the conformation and specificity of the pre-F and post-F probes using antibody binding assays and by staining B cells from antigen-experienced mice. The validated probes, in conjunction with a panel of B cell phenotypic markers, will allow us to interrogate B cell responses longitudinally for antibody repertoire and epitope-specific B cell phenotypes, and compare the responses between participants in the six arms of the clinical trial.