Preventive Vaccines for HIV

Franchini, Genoveffa

Abstract

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.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIABC011126-06
• Application #: 8763363
• Support Year: 6
• Fiscal Year: 2013
• Total Cost: $2,673,929

Institution

• Name: National Cancer Institute Division of Basic Sciences

Publications

Vaccari, Monica; Fourati, Slim; Gordon, Shari N et al. (2018) HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition. Nat Med 24:847-856

Auclair, Sarah; Liu, Fengliang; Niu, Qingli et al. (2018) Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. PLoS Pathog 14:e1006888

Vaccari, Monica; Gordon, Shari N; Fourati, Slim et al. (2016) Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition. Nat Med 22:762-70

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

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

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