The Virus Biology Scientific Research Support Component will provide molecular approaches, reagents and service to CHAVI-ID investigators geared toward determining whether T/F viruses have unique biological properties that can be exploited as targets for rational immunogen design. The overall goal is to understand the protective humoral, cellular and innate responses to HIV-1 infection, and to study the structural biology and virology of the T/F virus as a pathogen and immunogen. The Virus Biology Support Component will also explore the impact of Env quasispecies evolution on the development of broadly neutralizing antibodies and characterize human and primate vaccine breakthrough infections to determine whether certain vaccine modalities influence the number, composition, and phenotype of transmitted viruses.
Specific Aims Aim 1: Determine whether T/F viruses have common biological properties that comprise favorable targets for vaccine intervention Aim 2: Examine how the evolution of the Env quasispecies contributes to the development of broad neutralizing antibodies Aim 3: Genetically characterize SIV/SHIV challenge stocks and perform sieve analyses of breakthrough infections in actively or passively immunized primates Aim 4: Perform sieve analyses of breakthrough infections in vaccinated humans. These studies will support the B Cell Research Focus as well as Computational, Antibody Sequencing, Structural Biology, Neutralizing Antibodies and NHP SCRCs and will help to find new targets in the HIV-1 transmission pathway that will sharpen the focus of vaccine development efforts.

Public Health Relevance

The Virus Biology Support Component has developed a novel set of virological approaches that are geared toward identifying vulnerabilities of HI V-1 T/F viruses and their progeny that can be exploited for immunogen design. Using these novel approaches, the SRSC will provide expertise and generate a comprehensive set of well-characterized reagents that will contribute vitally to the objectives of the overall CHAVI-ID consortium.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
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
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
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
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:
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
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
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
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
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

Showing the most recent 10 out of 160 publications