The long-range objectives of Project 2 are to develop HlV-1 vaccine regimens that stimulate broadly directed immune responses and that block HIV-1 infection in humans and control viral replication In individuals who become infected. Although the precise correlates of immunity remain undefined, significant progress has been made in this area, and it appears that both humoral and cellular immune responses may be required for an optimal HIV-1 vaccine. In this project, we will test the hypothesis that mosaic antigens will induce increased breadth of cellular and/or humoral immune responses compared with natural sequence antigens in humans. We will also test the hypothesis that boosting responses primed with our optimal vector regimen with our stable clade 0 gp140 trimer will markedly augment antibody responses. To evaluate these hypotheses, we propose the following two Specific Aims:
Specific Aim 1 : To determine the optimal vector regimen in humans. Study IA: A phase 1 trial to compare natural and mosaic antigens in the context of Ad26/MVA vectors. Study IB: A phase 1 trial to compare the homologous Ad26 vector regimen with a heterologous Ad26/MVA vector regimen.
Specific Aim 2 : To determine the impact of a protein boost with our novel Env gpl40 trimer in humans. Study 2A: A phase 1 dose escalation trial of our novel trimeric Env gp140 protein. Study 2B: A phase 1 study to compare the best vector regimen with and without a protein trimer boost.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-EC-A)
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Beth Israel Deaconess Medical Center
United States
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Provine, Nicholas M; Larocca, Rafael A; Aid, Malika et al. (2016) Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells. J Immunol 197:1809-22
Provine, Nicholas M; Badamchi-Zadeh, Alexander; Bricault, Christine A et al. (2016) Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses. J Virol 90:4278-88
Barouch, Dan H; Ghneim, Khader; Bosche, William J et al. (2016) Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys. Cell 165:656-67
Handley, Scott A; Desai, Chandni; Zhao, Guoyan et al. (2016) SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination. Cell Host Microbe 19:323-35
Tartaglia, Lawrence J; Chang, Hui-Wen; Lee, Benjamin C et al. (2016) Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences. PLoS Pathog 12:e1005431
Mahan, Alison E; Jennewein, Madeleine F; Suscovich, Todd et al. (2016) Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. PLoS Pathog 12:e1005456
Borducchi, Erica N; Cabral, Crystal; Stephenson, Kathryn E et al. (2016) Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540:284-287
Penaloza-MacMaster, Pablo; Alayo, Quazim A; Ra, Joshua et al. (2016) Inhibitory receptor expression on memory CD8 T cells following Ad vector immunization. Vaccine 34:4955-63
Larocca, Rafael A; Abbink, Peter; Peron, Jean Pierre S et al. (2016) Vaccine protection against Zika virus from Brazil. Nature 536:474-8
Krishnamurthy, Siddharth R; Janowski, Andrew B; Zhao, Guoyan et al. (2016) Hyperexpansion of RNA Bacteriophage Diversity. PLoS Biol 14:e1002409

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