Abstract

The Science Core B will support activities in all four projects of this IPCAVD Proposal. Core B will be responsible for the production of protein reagents and vaccine immunogens that will be used in Projects One, Two, and Three. Core B will be responsible for the production of recombinant Envelope proteins for analytical studies in Project One, and the production of the Envelope-based immunogens that will be used in for pre-clinical vaccine studies in Project Two. Additionally, Core B will assist in the development of stable protein production cell lines and analytical validation of stably-produced Envelope immunogens in Project Three.

Public Health Relevance

Identifying immunogens and immunization protocols for the optimal stimulation of 'VRCOI-class' germline B cell receptors is one key first step toward generating broadly neutralizing antibodies against HIV by vaccination, and is crucial for the development of an effective vaccine against this virus. The studies in this proposal aim at developing Envelope immunogens that are optimized to engage and stimulate germline 'VRC01' class BCRs and to begin the first steps toward the development of broadly neutralizing activity, and eventually protection from infection with HIV-1. Thus, the activities in this proposal are highly relevant to the development of a universally effective HIV-1 vaccine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI109632-07
Application #
9645035
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2019-03-01
Budget End
2020-02-29
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Yacoob, Christina; Lange, Miles Darnell; Cohen, Kristen et al. (2018) B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques. PLoS Pathog 14:e1007120
Borst, Andrew J; Weidle, Connor E; Gray, Matthew D et al. (2018) Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core. Elife 7:
Escolano, Amelia; Dosenovic, Pia; Nussenzweig, Michel C (2017) Progress toward active or passive HIV-1 vaccination. J Exp Med 214:3-16
Horwitz, Joshua A; Bar-On, Yotam; Lu, Ching-Lan et al. (2017) Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo. Cell 170:637-648.e10
Escolano, Amelia; Steichen, Jon M; Dosenovic, Pia et al. (2016) Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice. Cell 166:1445-1458.e12
Yacoob, Christina; Pancera, Marie; Vigdorovich, Vladimir et al. (2016) Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors. Cell Rep 17:1560-1570
McGuire, Andrew T; Gray, Matthew D; Dosenovic, Pia et al. (2016) Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat Commun 7:10618
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
Dosenovic, Pia; von Boehmer, Lotta; Escolano, Amelia et al. (2015) Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice. Cell 161:1505-15
McGuire, Andrew T; Dreyer, Anita M; Carbonetti, Sara et al. (2014) HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. Science 346:1380-1383