This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dengue viruses are the most common cause of mosquito-borne viral disease in tropical and subtropical regions around the world. Although it is no longer endemic to the United States, sporadic cases do occur and epidemics are increasingly common in the Caribbean and along the southern border of the U.S. Antibody produced during dengue virus infection provides homotypic immunity. However, pre-existing, circulating antibodies can produce a non-protective antibody response that can intensify the course of disease in a subsequent heterotypic infection. Theoretically, an attenuated live virus or whole protein vaccine could lead to severe disease during a post-vaccination primary infection. An understanding of this antibody dependent enhancement phenomenon, as it occurs in humans, is critical to the development of vaccines that will provide long-term protection without increasing the risk of dengue hemorrhagic fever (DHF). To date, most published anti-dengue monoclonal antibodies (MAbs) are of mouse origin. However, mice are neither normal hosts for dengue virus nor do they develop severe infection, such as DHF, after inoculation. Therefore, these reagents may not reflect the repertoire and roles of antibody produced by humans during natural infection. Epstein-Barr Virus (EBV) transformation of B cells isolated from the peripheral blood of previously infected patients can be performed to develop cell lines which produce naturally occurring human monoclonal antibodies. Preliminary research by the candidate has successfully produced multiple such lines. The primary goals of the proposed research are to: 1. Increase our understanding of the human antibody response to dengue virus infection by creating a library of anti-dengue human monoclonal antibodies;2. Identify which antibodies are neutralizing or enhancing;3. Identify the epitopes that these antibodies target. This research is not only critical to the development of an effective and safe vaccine, but it will also provide a solid foundation for the candidate in the fields of virology and vaccine immunology. It is expected that the candidate will be ready to compete for independent federal funding within two to three years. Several available cores will be utilized to achieve these goals including the genomics, immunology sequencing, statistics and grants and contracts cores.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR021970-07
Application #
8360452
Study Section
Special Emphasis Panel (ZRR1-CR-B (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
7
Fiscal Year
2011
Total Cost
$204,195
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Rodriguez, Paulo C; Ochoa, Augusto C; Al-Khami, Amir A (2017) Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity. Front Immunol 8:93
Sanchez, Maria Dulfary; Ochoa, Augusto C; Foster, Timothy P (2016) Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways. Antiviral Res 132:13-25
Dai, Lu; Bai, Lihua; Lin, Zhen et al. (2016) Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus. Oncotarget 7:47052-47060
Schieffelin, John; Moses, Lina M; Shaffer, Jeffrey et al. (2016) Clinical validation trial of a diagnostic for Ebola Zaire antigen detection: Design rationale and challenges to implementation. Clin Trials 13:66-72
Fletcher, Matthew; Ramirez, Maria E; Sierra, Rosa A et al. (2015) l-Arginine depletion blunts antitumor T-cell responses by inducing myeloid-derived suppressor cells. Cancer Res 75:275-83
Dai, Lu; Trillo-Tinoco, Jimena; Bai, Aiping et al. (2015) Ceramides promote apoptosis for virus-infected lymphoma cells through induction of ceramide synthases and viral lytic gene expression. Oncotarget 6:24246-60
Geng, Degui; Kaczanowska, Sabina; Tsai, Alexander et al. (2015) TLR5 Ligand-Secreting T Cells Reshape the Tumor Microenvironment and Enhance Antitumor Activity. Cancer Res 75:1959-1971
Dai, Lu; Chen, Yihan; Bonstaff, Karlie et al. (2015) Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients. Cancer Lett 362:158-66
Dai, Lu; Trillo-Tinoco, Jimena; Cao, Yueyu et al. (2015) Targeting HGF/c-MET induces cell cycle arrest, DNA damage, and apoptosis for primary effusion lymphoma. Blood 126:2821-31
Dai, Lu; Cao, Yueyu; Chen, Yihan et al. (2015) Genomic analysis of xCT-mediated regulatory network: Identification of novel targets against AIDS-associated lymphoma. Oncotarget 6:12710-22

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