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.

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 #
5UM1AI100645-03
Application #
8681342
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Type
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
Chen, Shuobing; Wu, Jiayi; Lu, Ying et al. (2016) Structural basis for dynamic regulation of the human 26S proteasome. Proc Natl Acad Sci U S A 113:12991-12996
Tian, Ming; Cheng, Cheng; Chen, Xuejun et al. (2016) Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell 166:1471-1484.e18
Love, Tanzy M T; Park, Sung Yong; Giorgi, Elena E et al. (2016) SPMM: estimating infection duration of multivariant HIV-1 infections. Bioinformatics 32:1308-15
Barton, John P; Goonetilleke, Nilu; Butler, Thomas C et al. (2016) Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable. Nat Commun 7:11660
Astronomo, Rena D; Santra, Sampa; Ballweber-Fleming, Lamar et al. (2016) Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine 14:97-111
Herschhorn, Alon; Ma, Xiaochu; Gu, Christopher et al. (2016) Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins. MBio 7:
Theiler, James; Yoon, Hyejin; Yusim, Karina et al. (2016) Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. Sci Rep 6:33987
Ding, Shilei; Tolbert, William D; Prévost, Jérémie et al. (2016) A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability. J Virol 90:8395-409
Jeffries Jr, T L; Sacha, C R; Pollara, J et al. (2016) The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells. Mucosal Immunol 9:414-27
Abdul-Jawad, Sultan; Ondondo, Beatrice; van Hateren, Andy et al. (2016) Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition. Mol Ther 24:375-84

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