MLvax | Machine Learning-enabled Design of Prototype Pathogen Vaccines and Antibodies
University of Washington
Our proactive collaborative research network aims to develop generalizable strategies for safe and effective vaccines and monoclonal antibodies to combat high-priority pathogens most likely to threaten human health.
University of Washington
MLvax | Machine Learning-enabled Design of Prototype Pathogen Vaccines and Antibodies
A highly coordinated and synergistic Center that will develop end-to-end approaches and generalizable methods for designing potently protective vaccines against paramyxoviruses and bunyaviruses. Our Center brings together groups with world-leading expertise in computational protein design, structure-based vaccine design, mRNA vaccines, structural biology, viral entry, viral diversity and evolution, animal model development, high biosafety-level containment virology, vaccinology, and vaccine process development and technology transfer. Our Center will generate new knowledge, tools, and generalizable vaccine design approaches that will significantly advance vaccine development for pandemic preparedness generally, and will have a direct impact on public health through the development of antibody and vaccine candidates for several paramyxoviruses and bunyaviruses.
This Center is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number AI181881.
MLvax Overview
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MLvax Projects
Project 1: Computational Methods
PROJECT OVERVIEW:
Project 1 focuses on advancing cutting-edge computational methods to revolutionize vaccine and antibody design. By enhancing tools like RoseTTAFold2 and developing new machine-learning approaches, the team will predict and design precise structures for viral antigens, antibodies, and vaccines. These innovations will enable the creation of potent, broadly protective medical countermeasures and will be shared freely with the scientific community to accelerate global pandemic preparedness
LEAD ORGANIZATION/INSTITUTION:
University of Washington
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Lassa Virus, Rift Valley Fever Virus, Hendra Virus
Project 2: Viral Entry Antibodies and Structural Biology
PROJECT OVERVIEW:
Project 2 focuses on understanding viral glycoproteins and their interactions with receptors and antibodies to guide vaccine development. By studying key pathogens like henipaviruses, mammarenaviruses, and phenuiviruses, the project aims to map viral entry mechanisms and antibody responses to design potent, protective immunogens. This work will provide critical insights and tools to support the creation of vaccines and antiviral strategies across multiple research projects in the program.
LEAD ORGANIZATION/INSTITUTION:
University of Washington
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Lassa Virus, Rift Valley Fever Virus, Hendra Virus
Project 3: Antigen Design
PROJECT OVERVIEW:
Project 3 focuses on designing stabilized, native-like antigens for arenaviruses, phenuiviruses, and paramyxoviruses to drive the development of effective vaccines. Using advanced machine-learning techniques and deep mutational scanning, the project refines viral glycoproteins to improve stability, production, and immune response. By testing these designs in structural and immunological studies, the team will identify promising vaccine candidates that elicit potent neutralizing antibodies and protect against these high-priority viruses
LEAD ORGANIZATION/INSTITUTION:
University of Washington
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Lassa Virus, Rift Valley Fever Virus, Hendra Virus
Project 4: Protein Nanoparticle Vaccines
PROJECT OVERVIEW:
Project 4 focuses on creating innovative, protein nanoparticle vaccines for arenaviruses, phenuiviruses, and paramyxoviruses using cutting-edge machine learning tools for protein modeling and design. These vaccines will precisely display viral antigens in optimal arrangements to enhance immune responses. By rigorously testing these candidates in small and large animal models, the project aims to identify effective vaccine designs ready for further development, advancing global preparedness against these high-priority viruses
LEAD ORGANIZATION/INSTITUTION:
University of Washington
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Lassa Virus, Rift Valley Fever Virus, Hendra Virus
Project 5: mRNA and mRNA-launched Nanoparticle Vaccines
PROJECT OVERVIEW:
Project 5 aims to create advanced mRNA-based vaccines for arenaviruses, phenuiviruses, and paramyxoviruses by combining cutting-edge protein design with the rapid manufacturing capabilities of mRNA platforms. By integrating optimized antigens and innovative nanoparticle delivery, the project seeks to enhance vaccine potency and durability. This work will develop generalizable strategies that can be rapidly adapted to respond to future outbreaks, strengthening global pandemic preparedness.
LEAD ORGANIZATION/INSTITUTION:
University of Washington
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Lassa Virus, Rift Valley Fever Virus, Hendra Virus
MLvax Cores
Each ReVAMPP Center has an Administrative Core and a Data Management Core. Centers can also have up to three Scientific Cores to support resources and/or facilities that are essential for the collaborative research activities in two or more research projects.
CORE SERVICES:
Administrative
LEAD ORGANIZATION:
University of Washington
The Administrative Core is the central unit overseeing and supporting all Center components (five Projects, five Cores) and will ensure that the scientific team remains focused on the main goal of the Center: to develop generalizable strategies for paramyxovirus and bunyavirus vaccine design. The Core leadership will also ensure effective communication between other ReVAMPP Centers and the NIH. The goals of the Core will be: 1) to provide organizational governance and oversight to the Center, 2) to ensure effective and efficient communication and collaboration between the Center members, and 3) to maximize the engagement between our Center and the broader scientific community, including the other ReVAMPP Centers.
CORE SERVICES:
Data Stewardship
LEAD ORGANIZATION:
University of Washington
The Data Management Core (DMC) will create, operate, and maintain state-of-the-art computer systems to store and safeguard the diverse types of data generated by the Center, and develop protocols and interfaces to share those data between the institutions in the Center and the ReVAMPP Coordination and Data Sharing Center (CDSC). The DMC will follow the industry-standard and NIH-mandated security practices to manage access to the systems the team operates and all data backups, and the NIH FAIR data sharing principles to annotate newly generated data and make it available to others. The DMC will distribute the computational methods as free open-source software on GitHub to make the analyses reproducible and accelerate biological research worldwide.
CORE SERVICES:
Vaccine/Antibody Production
Manufacturing Process Development
LEAD ORGANIZATION:
University of Washington
The Vaccine Production and Process Development Core (Core C) will provide both high-throughput and scalable biologics production and characterization as well as comprehensive process development to support protein- and mRNA-based vaccine development in the Center and the broader ReVAMPP Network. In addition to the designed antigens and nanoparticle vaccines produced to support Projects in the Center, the Core will produce and provide to the ReVAMPP Network high-quality protein reagents such as monoclonal antibodies, viral entry receptors, and benchmark antigens to accelerate vaccine design and evaluation broadly. Core C will also perform detailed and comprehensive process development on Center lead vaccine candidates, building on a proven track record in translating innovative protein-based medicines and vaccines to industry and government partners.
CORE LEADERSHIP:
CORE SERVICES:
Animal Models
Correlates of Protection
LEAD ORGANIZATION:
University of Texas Medical Branch at Galveston
Core D provides approved Biosafety Level (BSL)-3/ABSL-3 and BSL-4/ABSL-4 facilities and a trained and highly experienced team of BSL-3 and BSL-4 investigators and staff to perform studies that support Center Projects 2-5. The services provided by Core D will include 1) a secure repository of well characterized seed stocks of viruses; 2) in vitro antiviral activity assays; 3) procurement of UTMB IACUC approval of animal protocols; 4) procurement, housing, and husbandry of animals; 5); development and/or optimization of animal models; 6) virus challenge, treatment, and collection of samples from animals; 7) technical expertise and equipment to conduct clinical pathological, immunological, and virological analyses; 8) histopathological analysis of tissues collected from infected animals; and 9) quality systems management of all records and data collected from animal studies.
CORE SERVICES:
Computational Analysis
Protein Engineering
LEAD ORGANIZATION:
Fred Hutchinson Cancer Center
Core E will use cutting-edge experimental and computational techniques to ensure that Center-developed vaccines target the full relevant evolutionary breadth of the prototype virus families, and to map the breadth and specificity of vaccine-elicited antibody responses. To do this, the Core will combine sequencing and phylogenetic analyses with deep mutational scanning to characterize viral diversity and its impact on the vaccines. For each prototype viral entry glycoprotein, the Core will create two types of libraries: phylogenetic libraries that contain variants spanning the natural diversity of that virus, and deep mutational scanning libraries that contain all amino-acid mutants of key representatives of each virus. Resulting information will inform the design and testing of the immunogens in the Center Projects.
MLvax Participating Organizations & Institutions
- Fred Hutch Cancer Center
- The University of Texas Medical Branch
- Washington University School of Medicine