Abstract

The overall goals of the CAVR Immunology Core are to provide a centralized resource for analysis of SIV- and SHIV-specific humoral immune responses in serum and mucosal specimens and to standardize the performance of flow cytometric assays that will be carried out by individual laboratories. A comprehensive range of well-standardized and quantitative assays of humoral immunity will be offerered, including a panel of complementary assays for the determination of neutralizing antibody responses and a newly developed assay that provides sensitive and reproducible determination of ADCC activity. To ensure consistent generation of polychromatic flow cytometry data and assays of cell-mediated immunity, the Immunology Core will coordinate the generation of consensus standard operating protocols (SOPs) for immunophenotyping and cytokine flow cytometry (CFC) assays, and supervise the implementation and validation of each SOP at each location.
Specific Aims i nclude: 1. To provide a centralized resource for the analysis of SIV/SHlV-specific antibodies in sera using ELISA and SIV/SHIV neutralization assays;2. To provide a centralized resource for analysis of SIV and SHIV-specific antibody responses in vaginal and rectal secretions;and 3. To ensure standardization of immunophenotyping and ICS assays conducted by different sites through the development of consensus protocols, implementation of proficiency testing, and comparative evaluation of flow cytometric data analysis. These activities will provide a comprehensive and robust assessment of host immune responses elicited by these vaccine approaches and will help define responses that are able to interrupt mucosal transmission of lentiviruses.

Public Health Relevance

Accurate and reproducible analysis of humoral and cellular immune responses is an essential step in the evaluation of candidate AIDS vaccines and efforts to understand mechanisms of immune protection against mucosal infection with SIV or SHIV. The Immunology Core will analyze virus-specific antibody responses in blood and mucosal secretions and ensure that assays conducted at different sites are reproducible and comparable.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI095985-03
Application #
8495250
Study Section
Special Emphasis Panel (ZAI1-LR-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$403,806
Indirect Cost
$44,112

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Okoye, Afam A; Hansen, Scott G; Vaidya, Mukta et al. (2018) Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat Med 24:1430-1440
Abbink, Peter; Larocca, Rafael A; Dejnirattisai, Wanwisa et al. (2018) Therapeutic and protective efficacy of a dengue antibody against Zika infection in rhesus monkeys. Nat Med 24:721-723
Walters, Lucy C; Harlos, Karl; Brackenridge, Simon et al. (2018) Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding. Nat Commun 9:3137
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
Barouch, Dan H; Thomas, Stephen J; Michael, Nelson L (2017) Prospects for a Zika Virus Vaccine. Immunity 46:176-182
Ackerman, Margaret E; Barouch, Dan H; Alter, Galit (2017) Systems serology for evaluation of HIV vaccine trials. Immunol Rev 275:262-270
McMichael, Andrew J; Picker, Louis J (2017) Unusual antigen presentation offers new insight into HIV vaccine design. Curr Opin Immunol 46:75-81
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
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:
Tomalka, Jeffrey; Ghneim, Khader; Bhattacharyya, Sanghamitra et al. (2016) The sooner the better: innate immunity as a path toward the HIV cure. Curr Opin Virol 19:85-91

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