Abstract

Project 3 is an integral part of our IPCAVD Program grant. We propose to produce cGMP grade Env immunogens (two) that will be evaluated clinically in a Phase I trial by the HIV Vaccine Trials Network. Our commerical partner in the GMP-production of our Env immunogens is ABL, Inc. (ABL). We developed a plan that ensures the most efficient transfer of materials and 'know how' In Env expression, purification and characterization (antigenicaily and immunogenically) from the Stamatatos lab to ABL. The Stamatatos lab and ABL will be In continuous communication to ensure the rapid resolution of any issues that may arise. The Stamatatos lab will verify and ensure that all Env-related products (intermediate and final) generated by ABL meet the required antigenic and immunogenic criteria our immunogens must meet before their clinical testing.The proposed strategy for the production of Env immunogens is based on the expertise of the Stamatatos lab in Env expression, purificaiton and characterization with ABL's expertise in large scale GMP manufacturing of proteins/drugs, including recombinant Env proteins.

  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 #
9645036
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