Abstract

Core A, the Immunogens and Formulations Core, will provide materials and expertise to all Projects in this grant. It will be responsible for obtaining making Gag proteins and native, glycosylated Envelope protein trimers to be used as boosting agents in rabbit and macaque experiments. These reagents are critical to the activities of all three Project teams. The Core has two Aims: 1) Express and purifiy Gag p24 proteins from patients in the study using E. coli expression systems. 2) Express and purify trimeric gp140 immunogens for vaccine studies in rabbits and macaques using mammalian cell expression systems (early and late proteins from up to six subjects). The proteins expressed in Aim 1will be used in proliferation assay in Project 2 to measure relative ability of patients to mount T helper responses to autologous Gag proteins in vitro. Glycoprotein Envelope trimers expressed in Aim 2 will serve as recombinant antigens for antibody assays in Projects 1 and 3, for T and B cell assays in Project 2, boosting agents for the DMAvaccines in rabbits (Project 3) and macaques (Project 3 and Core B).

Public Health Relevance

HIV vaccines that are effective in eliciting neutralizing antibodies are critically needed. This core will provide recombinant proteins to use in vaccine research.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI078064-02
Application #
8103006
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$224,432
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Type
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Nicholas, Katherine J; Flaherty, David K; Smith, Rita M et al. (2017) Chronic HIV-1 Infection Impairs Superantigen-Induced Activation of Peripheral CD4+CXCR5+PD-1+ Cells, With Relative Preservation of Recall Antigen-Specific Responses. J Acquir Immune Defic Syndr 74:72-80
Nicholas, Katherine J; Greenplate, Allison R; Flaherty, David K et al. (2016) Multiparameter analysis of stimulated human peripheral blood mononuclear cells: A comparison of mass and fluorescence cytometry. Cytometry A 89:271-80
Hessell, Ann J; Malherbe, Delphine C; Pissani, Franco et al. (2016) Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens. J Immunol 196:3064-78
Hessell, Ann J; Haigwood, Nancy L (2015) Animal models in HIV-1 protection and therapy. Curr Opin HIV AIDS 10:170-6
Sather, D Noah; Carbonetti, Sara; Malherbe, Delphine C et al. (2014) Emergence of broadly neutralizing antibodies and viral coevolution in two subjects during the early stages of infection with human immunodeficiency virus type 1. J Virol 88:12968-81
Cohen, Kristen; Altfeld, Marcus; Alter, Galit et al. (2014) Early preservation of CXCR5+ PD-1+ helper T cells and B cell activation predict the breadth of neutralizing antibody responses in chronic HIV-1 infection. J Virol 88:13310-21
Malherbe, Delphine C; Pissani, Franco; Sather, D Noah et al. (2014) Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol 88:12949-67
Pissani, Franco; Malherbe, Delphine C; Schuman, Jason T et al. (2014) Improvement of antibody responses by HIV envelope DNA and protein co-immunization. Vaccine 32:507-13
Nicholas, Katherine J; Zern, Emily K; Barnett, Louise et al. (2013) B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade. PLoS One 8:e84185
Pissani, Franco; Malherbe, Delphine C; Robins, Harlan et al. (2012) Motif-optimized subtype A HIV envelope-based DNA vaccines rapidly elicit neutralizing antibodies when delivered sequentially. Vaccine 30:5519-26

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