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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096040-02
Application #
8487359
Study Section
Special Emphasis Panel (ZAI1-EC-A)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$511,546
Indirect Cost
$132,222
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Aid, Malika; Abbink, Peter; Larocca, Rafael A et al. (2017) Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys. Cell 169:610-620.e14
Julg, Boris; Pegu, Amarendra; Abbink, Peter et al. (2017) Virological Control by the CD4-Binding Site Antibody N6 in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys. J Virol 91:
Penaloza MacMaster, Pablo; Shields, Jennifer L; Alayo, Quazim A et al. (2017) Development of novel replication-defective lymphocytic choriomeningitis virus vectors expressing SIV antigens. Vaccine 35:1-9
Julg, Boris; Liu, Po-Ting; Wagh, Kshitij et al. (2017) Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail. Sci Transl Med 9:
Barouch, Dan H; Thomas, Stephen J; Michael, Nelson L (2017) Prospects for a Zika Virus Vaccine. Immunity 46:176-182
Abbink, Peter; Larocca, Rafael A; Visitsunthorn, Kittipos et al. (2017) Durability and correlates of vaccine protection against Zika virus in rhesus monkeys. Sci Transl Med 9:
Ackerman, Margaret E; Barouch, Dan H; Alter, Galit (2017) Systems serology for evaluation of HIV vaccine trials. Immunol Rev 275:262-270
Xu, Ling; Pegu, Amarendra; Rao, Ercole et al. (2017) Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science 358:85-90
Keele, Brandon F; Li, Wenjun; Borducchi, Erica N et al. (2017) Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys. Nat Commun 8:15740
Julg, Boris; Tartaglia, Lawrence J; Keele, Brandon F et al. (2017) Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge. Sci Transl Med 9:

Showing the most recent 10 out of 65 publications