The long-range goal of this Program Project is to develop vaccine strategies and immunoprophylaxis against intrapartum transmission of HIV clade C by combining passive immunization with synergistic combinations of human neutralizing monoclonal antibodies with active vaccination with a DNA prime/protein boost strategy. The overall objectives for this Core are to provide the required experimental animals and support services needed to facilitate completion of the objectives outlined in Project 2 (Passive and Active Immunization) and Project 3 (DNA Prime/Protein Boost Vaccination). This will include provision of newborn and juvenile retrovirus-free (SIV/ STLV-1, SRV) rhesus macaques from the Yerkes macaque breeding colonies; oral and HIV macaques; immunizations of the experimental animals with DNA or protein immunogens; use of monoclonal antibodies alone or in combination with active immunization; viral challenge of the immunized animals; daily monitoring of the experimental animals; periodic physical examinations of the experimental animals and blood collections for hemogram and immunologic evaluations and for shipment to Drs. Ruprecht and Rasmussen's laboratories for in vitro studies; performance of CBCs and flow cytometry evaluations to determine lymphocyte subsets; and the performance of complete gross and histologic evaluation of all experimental animals that die or that are sacrificed during the course of the study. Provision of these resources and support services will facilitate the development and testing of the AIDS immunization strategies proposed in this Program Project. These studies will also document the infectivity and pathogenicity of the chimeric simian-human immunodeficiency virus encoding the env gene of HIV clade C, and will allow an assessment of vaccine efficacy with respect to either the prevention of infection (sterilizing immunity) or modification of post challenge virus load.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI048240-02
Application #
6474987
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2001-06-01
Project End
2002-05-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
$171,469
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
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
Bachler, Barbara C; Humbert, Michael; Lakhashe, Samir K et al. (2013) Live-virus exposure of vaccine-protected macaques alters the anti-HIV-1 antibody repertoire in the absence of viremia. Retrovirology 10:63

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