Approach 1: To validate the macaque model by reproducing vaccine efficacy similar to that observed in the RV144 HIV vaccine trial. Approach 2: To test the protective potential of CD8+ effector cells and antibodies in the genital and gastrointestinal tracts by using HPV based SIV vaccines and secreted gp96 Ig based SIV vaccines. Approach 3: To improve the efficacy of the ALVAC gp120 vaccine regimen by adding CD40L to the vectored vaccine, by changing the adjuvant in the protein boost, MF59 versus Alum, by using the CD4 gp120 FLSC immunogen that exposes cryptic epitopes, and by changing the priming Ad26 versus DNA versus ALVAC. Approach 4: To assess whether non-neutralizing antibodies are the mediators of protection from SIV and study the mechanism. Approach 5: To develop novel polypeptide vaccines for HIV to target seemingly protective epitopes. Approach 6: To assess whether complete protection from HIV/ SIV acquisition can be obtained with vaccination in combination with microbicides.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011126-06
Application #
8763363
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$2,673,929
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Moniuszko, Marcin; Liyanage, Namal P M; Doster, Melvin N et al. (2015) Glucocorticoid treatment at moderate doses of SIVmac251-infected rhesus macaques decreases the frequency of circulating CD14+CD16++ monocytes but does not alter the tissue virus reservoir. AIDS Res Hum Retroviruses 31:115-26
Gupta, Sandeep; Pegu, Poonam; Venzon, David J et al. (2015) Enhanced in vitro transcytosis of simian immunodeficiency virus mediated by vaccine-induced antibody predicts transmitted/founder strain number after rectal challenge. J Infect Dis 211:45-52
Vargas-Inchaustegui, Diego A; Tuero, Iskra; Mohanram, Venkatramanan et al. (2014) Humoral immunity induced by mucosal and/or systemic SIV-specific vaccine platforms suggests novel combinatorial approaches for enhancing responses. Clin Immunol 153:308-22
Fenizia, Claudio; Fiocchi, Martina; Jones, Kathryn et al. (2014) Human T-cell leukemia/lymphoma virus type 1 p30, but not p12/p8, counteracts toll-like receptor 3 (TLR3) and TLR4 signaling in human monocytes and dendritic cells. J Virol 88:393-402
Liyanage, Namal P M; Gordon, Shari N; Doster, Melvin N et al. (2014) Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac??? infection of macaques. Virology 450-451:359-68
Vaccari, Monica; Fenizia, Claudio; Ma, Zhong-Min et al. (2014) Transient increase of interferon-stimulated genes and no clinical benefit by chloroquine treatment during acute simian immunodeficiency virus infection of macaques. AIDS Res Hum Retroviruses 30:355-62
Teigler, Jeffrey E; Phogat, Sanjay; Franchini, Genoveffa et al. (2014) The canarypox virus vector ALVAC induces distinct cytokine responses compared to the vaccinia virus-based vectors MVA and NYVAC in rhesus monkeys. J Virol 88:1809-14
Sui, Yongjun; Hogg, Alison; Wang, Yichuan et al. (2014) Vaccine-induced myeloid cell population dampens protective immunity to SIV. J Clin Invest 124:2538-49
Vaccari, Monica; Halwani, Rabih; Patterson, L Jean et al. (2013) Antibodies to gp120 and PD-1 expression on virus-specific CD8+ T cells in protection from simian AIDS. J Virol 87:3526-37
Lugli, Enrico; Dominguez, Maria H; Gattinoni, Luca et al. (2013) Superior T memory stem cell persistence supports long-lived T cell memory. J Clin Invest 123:594-9

Showing the most recent 10 out of 12 publications