Scripps CHAVI-ID has been awarded $10.9 million in supplemental funding from the National Institutes of Health for Year 2 of the Center. The funding will provide support for projects at existing CHAVI-ID member institutions (The Rockefeller University, Beth Israel Deaconess Medical Center, and The Scripps Research Institute) and establish new collaborations with the Max Planck Institute for Infection Biology, Cornell University, International AIDS Vaccine Initiative, University of Massachusetts Medical School, Chinese Center for Disease Control, and Imperial College London.
Platform for the High Throughput Analysis of Antibody Responses
One project funded by the supplemental funds will focus on building a high throughput capability to analyze antibody responses. This capacity will allow researchers to rapidly complete a comprehensive characterization of broadly neutralizing antibody recognition of the HIV envelope spike to maximize the database used to guide immunogen design, rapidly analyze large numbers of antibody responses to immunogens in great depth to facilitate the iterative process that will likely be required for successful HIV vaccine design, and collect a vast database of antibody responses that will help reveal patterns in such responses and be valuable for interpreting the effects of immunization. Completion of this project will greatly accelerate multiple aims and advance iterative vaccine improvements.
Optimization of High Throughput Analysis for Human Specimens
This project will extend the automated direct cloning method (developed by Hedda Wardemann) to isolate monoclonal anitbodies from mice for use in analyzing human anti-HIV antibodies. This cutting-edge technology will greatly accelerate progress toward the established research goals of the Scripps CHAVI-ID.
High Throughput Genetic Analysis of Induced Antibody Responses
Iterative analysis of human and non-human primate antibody responses to rationally designed immunogens is a critical focus of the effort to identify and refine candidate HIV vaccines. With the supplemental funding, this project will establish the capacity to perform a detailed genetic analysis of antibody maturation. The sequencing equipment included in this project will enable exceptionally deep sequencing of the antibody repertoire across a large number of subjects. Computational antibodyomics analyses will be utilized to understand the mechanism of maturation porcesses underling the broadly neutralizing antibodies.
Titan Krios Electron Microscope
A state-of-the-art FEI Titan Krios will be purchased, with the help of matching funds and infrastructure investment from The Scripps Research Institute, and made available through the National Resource for Automated Molecular Microscopy (NRAMM), an NIH-funded program where use of imaging equipment and expertise are made available to the scientific research community as a public resource. This equipment will allow for the generation of high-resolution structures of HIV-1 Env trimers in order to inform vaccine design efforts, enhancing the chances of designs that truly emulate the natural epitopes in the context of the HIV-1 trimer. Combined with the superior reagents being generated within the Scripps CHAVI-ID, the group is now situated to make substantial breakthroughs that pertain to vaccine design and development.
Control of Virus by bnMAbs in NHP Models
An improved understanding of the virologic and immunologic parameters associated with immune correlates of protection is critical for the development of a highly efficacious prophylactic HIV-1 vaccine. To that end, this project will assess virologic and immunologic parameters in studies that will result in a deeper understanding of correlates of protection.
SOSIP BG505 Production
A significant overall scientific goal of the Scripps CHAVI-ID is "to design, engineer and produce a pure stable Env preparation that mimics the antigenic profile of the functional Env spike." Thanks to ongoing collaborations with HIVRAD and IAVI, BG505 SOSIP.664 gp140 has been identified as a superior candidate to meet this goal. Now, production of this trimer will move toward the GMP phase, thereby facilitating an experimental Phase I trial.