Standardized assessments of binding, neutralization, ADCC, and ADCVl effector activities of antibodies elicited by candidate HlV-1 Env immunogens are critical for informing HIV-1 vaccine design. Core B (Immune Monitoring Core) will provide standardized and validated GCLP humoral immune monitoring assay services for evaluating antibody responses elicited by Ad26/Ad26 and A26/MVA vector regimens with and without an Env gp140 trimer protein boost. We further propose to utilize additional assays for mapping the epitope specificities of NAb generated by these unique vaccine regimens. These services will provide critical support for Projects 1 and 2 by providing data that will help guide immunogen design and strategies for vaccine formulation and delivery.! We propose the following Specific Aims for Core B: 1. We will assess Env-specific antibody responses in subjects immunized with candidate HlV-1 Env immunogens for binding, neutralization, ADCC, and ADCVl effector activities. 2. We will utilize multiple assay formats for mapping the epitope specificities of antibodies elicited by vaccine regimens tested in Projects 1 and 2.

Public Health Relevance

The development of a preventative HlV-1 vaccine that can generate protective immunity remains a great scientific challenge. As novel Env immunogens enter preclinical and clinical testing', it is critical that optimized and validated in vitro assays are used to perform standardized measurements of vaccine-elicited antibody responses.

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 #
8487362
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
$115,719
Indirect Cost
$29,910
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Barouch, Dan H; Tomaka, Frank L; Wegmann, Frank et al. (2018) Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet 392:232-243
Martinot, Amanda J; Abbink, Peter; Afacan, Onur et al. (2018) Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys. Cell 173:1111-1122.e10
Badamchi-Zadeh, Alexander; Moynihan, Kelly D; Larocca, Rafael A et al. (2018) Combined HDAC and BET Inhibition Enhances Melanoma Vaccine Immunogenicity and Efficacy. J Immunol 201:2744-2752
Iampietro, M Justin; Larocca, Rafael A; Provine, Nicholas M et al. (2018) Immunogenicity and Cross-Reactivity of Rhesus Adenoviral Vectors. J Virol 92:
Badamchi-Zadeh, Alexander; Tartaglia, Lawrence J; Abbink, Peter et al. (2018) Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice. J Virol 92:
Bricault, Christine A; Kovacs, James M; Badamchi-Zadeh, Alexander et al. (2018) Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J Virol :
Whitney, James B; Lim, So-Yon; Osuna, Christa E et al. (2018) Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy. Nat Commun 9:5429
Baden, Lindsey R; Walsh, Stephen R; Seaman, Michael S et al. (2018) First-in-Human Randomized, Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector. J Infect Dis 218:633-644
Borducchi, Erica N; Liu, Jinyan; Nkolola, Joseph P et al. (2018) Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature 563:360-364
Blass, Eryn; Aid, Malika; Martinot, Amanda J et al. (2018) Adenovirus Vector Vaccination Impacts NK Cell Rheostat Function following Lymphocytic Choriomeningitis Virus Infection. J Virol 92:

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