PROVIDENT | Prepositioning Optimized Strategies for Vaccines and Immunotherapeutics against Diverse Emerging Infectious Threats
Albert Einstein College of Medicine
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.
Albert Einstein College of Medicine
PROVIDENT | Prepositioning Optimized Strategies for Vaccines and Immunotherapeutics against Diverse Emerging Infectious Threats
The PROVIDENT consortium will develop vaccines and treatments against three different families of viruses that contain many epidemic and pandemic threats. Our goal is to create approaches to vaccination that are generalizable, so that they can be quickly applied to develop a vaccine against a related but distinct outbreak virus.
This Center is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number AI181977.
PROVIDENT Overview
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| Vaccine Approaches | Antibody Approaches |
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PROVIDENT Projects
Project 1: Discovery and Dissection of Virus-host Interactions and Pathogenetic Mechanisms
PROJECT OVERVIEW:
Project 1 aims to uncover how viruses like Crimean-Congo hemorrhagic fever virus (CCHFV), Andes virus (ANDV), and Menangle virus (MenPV) interact with host cells to cause disease. Using advanced genetic and proteomic tools, the team will identify key host factors these viruses exploit and understand their roles in infection and pathogenesis. This work will generate critical insights to support the development of vaccines and therapies while enhancing preparedness against these and related viruses.
LEAD ORGANIZATION/INSTITUTION:
Albert Einstein College of Medicine
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Andes Virus, Crimean-Congo Hemorrhagic Fever Virus, Menangle Virus
Project 2: Antigen Design and Immunological Evaluation
PROJECT OVERVIEW:
Project 2 focuses on designing optimized vaccine antigens to protect against nairoviruses, hantaviruses, and paramyxoviruses with pandemic potential. Using advanced antigen engineering and structural biology, the project will refine vaccine candidates through iterative testing of immunogenicity and efficacy in animal models. These efforts will create a blueprint for developing vaccines against diverse viruses within these families, advancing preparedness for emerging infectious threats.
LEAD ORGANIZATION/INSTITUTION:
University of New Mexico
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Andes Virus, Crimean-Congo Hemorrhagic Fever Virus, Menangle Virus
Project 3: Rapid-Response Roadmap for RNA Vaccines
PROJECT OVERVIEW:
Project 3 aims to enhance RNA vaccine strategies for nairoviruses, hantaviruses, and paramyxoviruses by optimizing antibody responses, exploring multi-antigen vaccine designs, and analyzing innate immune responses and reactogenicity. By leveraging advanced methodologies and next-generation RNA platforms, the project seeks to refine vaccine efficacy and safety. These findings will inform the design of effective, safe, and rapid-response vaccines for nairoviruses, hantaviruses, paramyxoviruses, and other viruses with pandemic potential, equipping developers with tools and strategies for future outbreaks.
LEAD ORGANIZATION/INSTITUTION:
Hdt Bio
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Andes Virus, Crimean-Congo Hemorrhagic Fever Virus, Menangle Virus
Project 4: Mining Human Antibody Responses to Inform Vaccine and Therapeutic Design
PROJECT OVERVIEW:
Project 4 focuses on developing a rapid and comprehensive platform for identifying, optimizing, and producing monoclonal antibodies (mAbs) to combat nairoviruses, hantaviruses, and paramyxoviruses. By profiling immune responses in naive and convalescent donors, the team will identify and engineer high-affinity, broadly protective mAbs, using advanced technologies like memory B cell sorting, deep mutational scanning, and machine learning algorithms. This project aims to enhance our understanding of antibody-antigen interactions, design antibody cocktails that address viral escape mechanisms, and optimize mAbs for efficient production and stability. These efforts will inform the design of next-generation vaccines and provide a robust framework for rapidly responding to emerging viral threats.
LEAD ORGANIZATION/INSTITUTION:
Houston Methodist Hospital
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Andes Virus, Crimean-Congo Hemorrhagic Fever Virus, Menangle Virus
PROVIDENT 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:
Albert Einstein College of Medicine
The Administrative Core serves as the hub for PROVIDENT, providing governance, personnel, and resources for all program management arms. Albert Einstein College of Medicine (Einstein) will serve as the lead institution for PROVIDENT. To achieve these goals and advance PROVIDENT's strategic research plan, the Administrative Core will develop and implement plans to: (1) organize, oversee, monitor, and report Center activities; (2) oversee and facilitate data sharing with the ReVAMPP Network and the public; (3) foster team interaction and coordination; (4) communicate the Center's mission and activities to the scientific community and the public; and (5) manage travel, conflict, change, risk, intellectual property, human subjects and animals, resources, reagents, and regulatory challenges.
CORE SERVICES:
Data Stewardship
LEAD ORGANIZATION:
Albert Einstein College of Medicine
The Data Core has a holistic data management approach that defines and adopts best practices to be implemented across the Center to to maximize data and resource accessibility in a standardized, organized, secure, reproducible, confidential, and flexible manner and to establish central platforms promoting collaboration, cooperation, and streamlined knowledge transfer.
CORE SERVICES:
Structure Analysis
Protein Engineering
Vaccine/Antibody Production
LEAD ORGANIZATION:
University of Texas at Austin
The Structure and Protein Engineering Core provides services encompassing protein engineering and production, characterization, and structural biology. Core C will perform high-throughput protein engineering and production, allowing hundreds of designed protein constructs to be biophysically characterized for thermal stability, conformational homogeneity, and antibody reactivity.
CORE SERVICES:
Animal Models
Correlates of Protection
LEAD ORGANIZATION:
U.S. Army Medical Research Institute of Infectious Diseases
Core D is responsible for providing Center Research Projects animal model testing support required for the validation of newly identified host factors and novel medical countermeasures (MCMs) against hantaviruses, nairoviruses, and paramyxoviruses. In vivo efficacy testing is essential for the down-selection, evaluation, and development of potent and effective MCMs, especially given that many aspects of viral replication and pathogenesis cannot be faithfully recapitulated in vitro. Core D will also support the development of animal-based tools, including genome-edited murine and Syrian hamsters that will be used to generate novel rodent models of disease and interrogate fundamental viral-host factor interactions. In addition to animal model development and rodent efficacy studies, Core D will support immunogenicity testing in non-human primates to assess lead mRNA vaccine candidates and provide supporting data for pre-clinical or phase I trials.
CORE SERVICES:
Manufacturing Process Development
Vaccine/Antibody Production
LEAD ORGANIZATION:
Houston Methodist Hospital
The RNA Manufacturing Core will support Center Projects by generating RNA for their potential engineering and screening. Once a lead antigen is selected, the Core will generate both mRNA and self-amplifying replicon mRNA (repRNA) encoding the same antigens to compare the safety and effectiveness of the immune response to the two different RNA vaccine platforms. To continue to innovate and improve mRNA and repRNA platforms to reduce reactogenicity, increase stability, and enhance translational efficiency of the RNA constructs, the Core will prepare antigen gene sequences with alternative, artificial intelligence-guided codon usage, and incorporate novel lipids into the lipid nanoparticles.
PROVIDENT Participating Organizations & Institutions
- Albert Einstein College of Medicine
- HDT Bio
- Houston Methodist Hospital
- The University of New Mexico
- The University of Texas at Austin
- U.S. Army Medical Research Institute of Infectious Diseases
- University of California, Berkeley