The acquired immunodeficiency syndrome (AIDS) caused by HIV-1 is the fourth leading cause of death worldwide. Development of an effective vaccine against HIV/AIDS is the long term solution to this problem. The failure of Merck's adenovirus type 5 (Ad5) based HIV-1 clade B vaccine in humans that is designed to elicit primarily antiviral T cells strongly suggests the need to develop novel vaccine approaches that generate high levels of anti-viral T cells with improved function as well as protective Ab. The goal of this HIVRAD is to generate high levels of broadly cross-reactive antiviral T cells with enhanced proliferative/protective phenotype and high avidity antiviral binding Ab by targeting CD40 and mTOR (mammalian target of rapamycin) pathways. The overall goal of this administrative core is to provide coordination between projects 1 and 2, and core B, and help with data management and data analyses. This Administrative Core has the following six specific aims: (1) Provide overall coordination for the Program. (2) Provide data management and statistical support. (3) Provide logistical support for intellectual property filings and negotiations. (4) Assist with publications. (5) Maintain budgets and fiscal oversight. (6) Provide vaccines and peptides

Public Health Relevance

WHO estimates that there are currently 32 million humans living with HIV/AIDS. Drugs and improved treatment regimens have successfully prolonged the lives of infected individuals in first world countries. However, these are not affordable for the vast majority of HIV-infected individuals. Even in developed nations these are limited by toxicity, affordability, the need for rigorous adherence to therapy and the emergence of drug resistant viruses. Thus, there is a great need to develop a safe and effective HIV vaccine that provides a low-cost, lowtoxicity solution to long-term control of viral replication - the main goal of this PPG.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI088575-04
Application #
8662366
Study Section
Special Emphasis Panel (ZAI1-RB-A (J1))
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$323,012
Indirect Cost
$150,084
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Velu, Vijayakumar; Mylvaganam, Geetha Hanna; Gangadhara, Sailaja et al. (2016) Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues during Chronic Simian Immunodeficiency Virus Infection Defines Functionally Distinct Germinal Center Tfh Cells. J Immunol 197:1832-42
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 TRIM5α-Restrictive Macaques. J Immunol 197:3586-3596
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
Iyer, Smita S; Gangadhara, Sailaja; Victor, Blandine et al. (2015) Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques. J Immunol 195:994-1005
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
Mylvaganam, Geetha H; Velu, Vijayakumar; Hong, Jung-Joo et al. (2014) Diminished viral control during simian immunodeficiency virus infection is associated with aberrant PD-1hi CD4 T cell enrichment in the lymphoid follicles of the rectal mucosa. J Immunol 193:4527-36
Kwa, Suefen; Lai, Lilin; Gangadhara, Sailaja et al. (2014) CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus SIV239 vaccine enhances SIV-specific humoral and cellular immunity and improves protection against a heterologous SIVE660 mucosal challenge. J Virol 88:9579-89
Araki, Koichi; Youngblood, Ben; Ahmed, Rafi (2013) Programmed cell death 1-directed immunotherapy for enhancing T-cell function. Cold Spring Harb Symp Quant Biol 78:239-47
Xu, Xiaojin; Ye, Lilin; Araki, Koichi et al. (2012) mTOR, linking metabolism and immunity. Semin Immunol 24:429-35
Araki, Koichi; Ellebedy, Ali H; Ahmed, Rafi (2011) TOR in the immune system. Curr Opin Cell Biol 23:707-15

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