? CORE B The major objective for Core B (Virology/Immunology) is to support Projects 1, 2 and 3 as well as Cores C and D of this HIVRAD Program Project with extensive virology and immunology expertise. Core B will provide standardized reagents, assays and analyses in order to achieve inter-project data consistency and cross- reference. Core B will produce, characterize and standardize stocks of recombinant simian-human immunodeficiency viruses (SHIVs), SHIV-1157ipEL-p and SHIV-1157ipd3N4, for in vitro and in vivo studies of Projects 1, 2 and 3, and Cores C and D. To allow high-throughput screening, Core B will use infectious molecular clones (IMCs) containing the Renilla luciferase reporter gene (LucR IMCs) along with env genes derived from SHIV-1157ipEL and SHIV-1157ipd3N4. Core B contains a subcontract with the Institute for Research in Biomedicine (IRB), Bellinzona, Switzerland, headed by Dr. Antonio Lanzavecchia; this subcontract will generate monoclonal antibodies (mAbs) as IgG1, dimeric IgA1 (dIgA1) and dIgA2 versions for Projects 1 and 2 as well as for Cores C and D. Using standardized and uniform assays, Core B will support the Program Project by measuring humoral and cellular immune responses, including neutralizing antibody (nAb) titers in plasma and mucosal secretions. Core B will perform neutralization assays, ELISPOT assays for various cytokines, B-cell ELISPOTs, CFSE-based antigen-specific T-cell proliferation and intracellular cytokine staining. Core B also will conduct routine monitoring of all the SHIV-challenged animals for plasma viral RNA and proviral DNA loads and T-cell subsets. To provide support to all scientific components of the Program Project, Core B's Specific Aims are: 1. To produce and characterize virus stocks for in vitro assays as well as stocks of SHIV-1157ipEL-p (tier 1) and SHIV-1157ipd3N4 (tier 2) for challenge studies in rhesus monkeys (RMs). 2. To generate, produce, purify and characterize all mAbs as dIgA1, dIgA2 and IgG1 versions for passive immunization and imaging experiments in RMs. 3. To monitor humoral and cellular immune responses of experimental animals. 4. To monitor the infection status of all experimental RMs in Core C.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI048240-12A1
Application #
9111605
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2000-09-30
Project End
2021-06-30
Budget Start
2016-07-13
Budget End
2017-06-30
Support Year
12
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Tokatlian, Talar; Kulp, Daniel W; Mutafyan, Andrew A et al. (2018) Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci Rep 8:16527
Ruprecht, Ruth M; Lakhashe, Samir K (2017) Antibody-mediated immune exclusion of HIV. Curr Opin HIV AIDS 12:222-228
Ruprecht, Ruth M (2017) Anti-HIV Passive Immunization: New Weapons in the Arsenal. Trends Microbiol 25:954-956
Schneider, Jeffrey R; Carias, Ann M; Bastian, Arangaserry R et al. (2017) Long-term direct visualization of passively transferred fluorophore-conjugated antibodies. J Immunol Methods 450:66-72
Kulkarni, Viraj; Ruprecht, Ruth M (2017) Mucosal IgA Responses: Damaged in Established HIV Infection-Yet, Effective Weapon against HIV Transmission. Front Immunol 8:1581
Sholukh, Anton M; Watkins, Jennifer D; Vyas, Hemant K et al. (2015) Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge. Vaccine 33:2086-95
Lakhashe, Samir K; Byrareddy, Siddappa N; Zhou, Mingkui et al. (2014) Multimodality vaccination against clade C SHIV: partial protection against mucosal challenges with a heterologous tier 2 virus. Vaccine 32:6527-36
Zhou, Mingkui; Ruprecht, Ruth M (2014) Are anti-HIV IgAs good guys or bad guys? Retrovirology 11:109
Sholukh, Anton M; Byrareddy, Siddappa N; Shanmuganathan, Vivekanandan et al. (2014) Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose. Retrovirology 11:8
Watkins, Jennifer D; Sholukh, Anton M; Mukhtar, Muhammad M et al. (2013) Anti-HIV IgA isotypes: differential virion capture and inhibition of transcytosis are linked to prevention of mucosal R5 SHIV transmission. AIDS 27:F13-20

Showing the most recent 10 out of 77 publications