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 #
1U19AI096040-01A1
Application #
8393817
Study Section
Special Emphasis Panel (ZAI1-EC-A (M2))
Project Start
Project End
Budget Start
2012-06-13
Budget End
2013-05-31
Support Year
1
Fiscal Year
2012
Total Cost
$122,661
Indirect Cost
$22,661
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:

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