Memory B cells are key contributors to the indiction and maintenance of humoral immunity. Characterization of the memory B cells response to SIV will be important in an vaccine strategy to elicit a neutralizing antibody response. In this research application we propose to develop reagents to specifically identify macaque memory B cell populations. In proof of principle studies we have produced monoclonal lamprey VLR antibodies that are specific for memory B cells in humans. We propose to develop novel monoclonal VLR antibodies to macaque memory B cells. Unlike mammalian antibodies, the VLR antibodies of the jawless sea lampreys utilize leucine-rich repeats as basic structural units. The radically different protein architecture combined with the large evolutionary distance ofthe sea lamprey allows VLR antibodies to be made that recognize antigenic structures which are not detetcted by mammalian immunoglobulin-based antibodies for structural or tolerogenic reasons. To generate monoclonal VLR antibodies, we will immunize sea lamprey larvae with purified primary B cells or B cell lines. VLR antibody expression libraries will be screened by flow cytometry and monoclonal VLR antibodies that specifically interact with memory B cells or subpopulations thereof will be used as affinity reagents to identify the antigen recognized by the VLR antibody. The VLR antibodies from this core will be provided to research groups to analyze the memory B cell responses to vaccination or SIV challenge. In a complementary approach, we will generate conventional mammalian monoclonal antibodies to FCRL4, an immunoreceptor that In humans is expressed by a subpopulation of mucosa associated memory B cells with enrichment in antibody specificity for the HIV gp120 protein. A fusion protein consisting ofthe extracellular domain of FCRL4 fused to the Fc-domain of IgG will serve as the immunogen and the specific monoclonal antibodies will be identified by flow cytometry. The long term goal of these studies is to generate novel reseach reagents that will facilitate the analysis of memory B cells responding to SIV challenge or vaccination.
The goal of this project is generation of novel monoclonal antibodies that allow identification of memory B cells responding to vaccination or infection with pathogens. These studies will aid in the generation and evaluation of vaccines that can elicit protective antibody production.
|Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja et al. (2016) Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine. Open Forum Infect Dis 3:ofw034|
|Smith, S Abigail; Kilgore, Katie M; Kasturi, Sudhir Pai et al. (2016) Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques. J Virol 90:1880-7|
|Locci, Michela; Wu, Jennifer E; Arumemi, Fortuna et al. (2016) Activin A programs the differentiation of human TFH cells. Nat Immunol 17:976-84|
|Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja et al. (2016) High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5Î±-Restrictive Macaques. J Immunol 197:3586-3596|
|Cho, Alice; Wrammert, Jens (2016) Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine. Curr Opin Virol 17:110-5|
|Yu, Cuiling; Liu, Yanling; Chan, Justin Tze Ho et al. (2016) Identification of human plasma cells with a lamprey monoclonal antibody. JCI Insight 1:|
|Havenar-Daughton, Colin; Reiss, Samantha M; Carnathan, Diane G et al. (2016) Cytokine-Independent Detection of Antigen-Specific Germinal Center T Follicular Helper Cells in Immunized Nonhuman Primates Using a Live Cell Activation-Induced Marker Technique. J Immunol 197:994-1002|
|Kilgore, Katie M; Murphy, Megan K; Burton, Samantha L et al. (2015) Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope. J Virol 89:8130-51|
|Chamcha, Venkateswarlu; Jones, Andrew; Quigley, Bernard R et al. (2015) Oral Immunization with a Recombinant Lactococcus lactis-Expressing HIV-1 Antigen on Group A Streptococcus Pilus Induces Strong Mucosal Immunity in the Gut. J Immunol 195:5025-34|
|Kwa, Suefen; Sadagopal, Shanmugalakshmi; Shen, Xiaoying et al. (2015) CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus (SIV) vaccine enhances protection against neutralization-resistant mucosal SIV infection. J Virol 89:4690-5|
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