Abstract

The goal of the Nonhuman Primate Support Component is to support the overall program of the CHAVI-ID by performing in vivo passive protection or enhancement studies to characterize the functional activities of mAbs generated by CHAVI-ID investigators, by performing immunization studies with novel immunogens developed by CHAVI investigators, and performing correlative mAb and immune functional studies to use the rhesus monkey as a model to accelerate HlV-1 vaccine development. This work will be facilitated by recent advances we have made in a number of complementing areas, including the development of novel mucosal SIV/SHIV challenge models, novel SHIV constructs expressing transmitted/founder HlV-1 envelopes, adjuvants that substantially increase the immunogenicity of HlV-1 envelope protein immunogens, and recombinant technology for generating monoclonal antibodies from immunized rhesus macaques.
Specific Aims Aim 1. Pursue passive protection studies in rhesus macaques to determine the effectiveness of antibodies with defined specificities and CD8 T cell-produced factors in blocking SHIV/SIV mucosal acquisition.
Aim 2. Perform immunization studies in rhesus macaques to explore novel strategies for vaccine induction of antibodies that might protect against HIV-1 acquisition.
Aim 3. Explore the evolution of broadly neutralizing anti-HIV-1 antibodies in vaccinated rhesus macaques.

Public Health Relevance

Vaccine strategies aimed at preventing mucosal HIV-1 acquisition are needed. The nonhuman primate system an important model system to guide optimal strategies to induce the immune system to make protective immune responses to HIV-1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
1UM1AI100645-01
Application #
8385857
Study Section
Special Emphasis Panel (ZAI1-JBS-A (M1))
Project Start
Project End
Budget Start
2012-07-15
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$2,700,027
Indirect Cost
$661,686

  Institution

Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Castillo-Menendez, Luis R; Witt, Kristen; Espy, Nicole et al. (2018) Comparison of Uncleaved and Mature Human Immunodeficiency Virus Membrane Envelope Glycoprotein Trimers. J Virol 92:
Brown, Eric P; Weiner, Joshua A; Lin, Shu et al. (2018) Optimization and qualification of an Fc Array assay for assessments of antibodies against HIV-1/SIV. J Immunol Methods 455:24-33
Finney, Joel; Yeh, Chen-Hao; Kelsoe, Garnett et al. (2018) Germinal center responses to complex antigens. Immunol Rev 284:42-50
Pardi, Norbert; Hogan, Michael J; Naradikian, Martin S et al. (2018) Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med 215:1571-1588
Eudailey, Joshua A; Dennis, Maria L; Parker, Morgan E et al. (2018) Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques. mSphere 3:
Kelsoe, Garnett; Haynes, Barton F (2018) What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling. Cold Spring Harb Perspect Biol 10:
Wagh, Kshitij; Kreider, Edward F; Li, Yingying et al. (2018) Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth. Cell Rep 25:893-908.e7
Fu, Qingshan; Shaik, Md Munan; Cai, Yongfei et al. (2018) Structure of the membrane proximal external region of HIV-1 envelope glycoprotein. Proc Natl Acad Sci U S A 115:E8892-E8899
Fera, Daniela; Lee, Matthew S; Wiehe, Kevin et al. (2018) HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope. Nat Commun 9:1111
McMichael, Andrew J (2018) Is a Human CD8 T-Cell Vaccine Possible, and if So, What Would It Take? Could a CD8+ T-Cell Vaccine Prevent Persistent HIV Infection? Cold Spring Harb Perspect Biol 10:

Showing the most recent 10 out of 261 publications