R2P2 | Vaccines and Therapeutic Antibodies to Respiro, Rubula, Peribunya and Phenuiviridae
Washington University in St. Louis
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.
Washington University in St. Louis
R2P2 | Vaccines and Therapeutic Antibodies to Respiro, Rubula, Peribunya and Phenuiviridae
The R2P2 ReVAMPP Center aims to develop vaccines and antibody-based treatments for viruses in the Paramyxoviridae, Peribunyaviridae, and Phleboviridae families. The center focuses on four primary research projects, working alongside key scientific cores to investigate prototype viruses and use principles of reverse vaccinology to understand immunity and antigenicity. The projects compare three vaccine platforms (protein subunit, mRNA, and chimeric VSV) to gather information about their performance in translating to related pathogens.
This Center is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number AI181984.
R2P2 Overview
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| Vaccine Approaches | Antibody Approaches |
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R2P2 Projects
Project 1: Prototype Strategies for Antibodies and Vaccines for Respiroviruses
PROJECT OVERVIEW:
Project 1 focuses on advancing vaccines and therapeutic antibodies against respiroviruses, using human parainfluenza virus type 3 (HPIV3) as the prototype due to its well-characterized surface proteins, HN and F. By studying the structure-function relationships of these proteins with cutting-edge techniques like cryo-EM, the team aims to identify optimal antigenic targets and design effective immunogens. The project evaluates three vaccine platforms--subunit, mRNA, and rVSV--while also developing monoclonal antibodies with high resistance barriers, iteratively refining designs to ensure broad applicability to related viruses like HPIV1. These efforts will define effective vaccines and therapeutic strategies for respiroviruses and other paramyxoviruses with pandemic potential.
LEAD ORGANIZATION/INSTITUTION:
Columbia University
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Human Parainfluenza Viruses 3
TEST CASE VIRUSES:
- Human Parainfluenza Viruses 1
Project 2: Prototype Strategy for Vaccines and Antibodies to Rubulaviruses
PROJECT OVERVIEW:
Project 2 focuses on advancing vaccines and antibodies against highly transmissible rubulaviruses, using mumps virus (MuV) as a prototype. By studying the structure and function of the F and HN glycoproteins, the team aims to design stabilized immunogens and evaluate their efficacy across three vaccine platforms: soluble-adjuvated proteins, mRNA, and replication-competent rVSV. The project also isolates and characterizes monoclonal antibodies to enhance immunogen design and assess their protective capabilities in animal models. This work not only informs next-generation vaccine and therapeutic strategies but also prepares for potential pandemic threats from related pre-spillover rubulaviruses.
LEAD ORGANIZATION/INSTITUTION:
University of Pittsburgh
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Mumps Virus
TEST CASE VIRUSES:
- Bat Mumps Virus
Project 3: Prototype Strategy for Vaccines and Antibodies to Peribunyaviridae
PROJECT OVERVIEW:
Project 3 aims to develop generalizable vaccine strategies and therapeutic monoclonal antibodies (mAbs) against peribunyaviruses, using Oropouche virus (OROV) as the prototype and La Crosse virus (LACV) for validation. By stabilizing the pre-fusion form of the class II fusion protein Gc and analyzing the structure and function of viral entry proteins Gn and Gc, the project identifies optimal targets for vaccines and antibodies. Leveraging convalescent human mAbs and advanced vaccine platforms, including protein subunit, mRNA-LNP, and VSV-vectored approaches, the team rigorously tests efficacy in small animal models. Close collaboration with related studies ensures synergy and rapid progress, advancing pandemic preparedness against peribunyaviruses and related viral threats.
LEAD ORGANIZATION/INSTITUTION:
Washington University in St. Louis
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Oropouche Virus
TEST CASE VIRUSES:
- La Crosse Virus
Project 4: Design and Development of Generalizable Countermeasures Against Prototype Phenuiviruses
PROJECT OVERVIEW:
Project 4 focuses on developing generalizable vaccines and therapeutic antibodies for phenuiviruses, using Rift Valley fever virus (RVFV) and Toscana virus (TOSV) as prototypes. By studying the structure and function of their glycoproteins (Gn/Gc), the project aims to identify commonalities that inform immunogen design and therapeutic targeting, with further validation on a distantly related phenuivirus, SFTSV. Through parallel approaches and advanced platforms like mRNA and VSV-based vaccines, the team seeks to establish a broadly applicable framework for combating current and future phenuivirus threats. This work advances the field by creating a scalable strategy for pandemic preparedness against these high-priority pathogens.
LEAD ORGANIZATION/INSTITUTION:
University of Pittsburgh
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Rift Valley Fever Virus, Toscana Virus
TEST CASE VIRUSES:
- Severe Fever With Thrombocytopenia Syndrome Virus
R2P2 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:
Washington University in St. Louis
The Administrative Core A serves as the hub of coordination and management for the R2P2 ReVAMPP Center, driving its mission to advance vaccines and therapeutics against critical viral threats. Led by an experienced leadership team, the Core facilitates strategic decision-making, fosters collaboration among projects and cores, and ensures compliance and financial accountability. By integrating input from the Scientific Advisory Board, NIAID, and industry partners, the Core supports a clear path from research to product development. Through robust oversight and communication, the Administrative Core ensures the success of the Center's innovative and impactful goals.
CORE SERVICES:
Data Stewardship
Computational Analysis
LEAD ORGANIZATION:
Washington University in St. Louis
The Data Management Core B serves as the central hub for data integration, analysis, and sharing across the R2P2 ReVAMPP Center, enabling seamless collaboration among projects and scientific cores. By leveraging WUVAX, a cutting-edge cloud-based system, the Core ensures real-time access to integrated datasets, progress metrics, and documentation through a user-friendly interface. This innovative approach enhances data efficiency, transparency, and connectivity while providing robust analytical support using advanced statistical and machine-learning methods. Core B plays a pivotal role in advancing the Center's mission by facilitating data-driven insights and broad dissemination within the ReVAMPP network and the scientific community.
CORE SERVICES:
Structure Analysis
Protein Engineering
LEAD ORGANIZATION:
University of Texas at Austin
Structure plays a critical role in the R2P2 ReVAMPP Center by using structural biology to guide the design of vaccine antigens and monoclonal antibodies against paramyxoviruses and bunyaviruses. Led by experts in structural virology, the Core provides atomic-level insights into viral glycoproteins, enabling rational antigen design and evaluation to elicit optimal immune responses. Through advanced techniques like X-ray crystallography, cryo-EM, and biophysical characterization, Core C supports the creation of high-quality vaccine antigens and antibody candidates. These efforts drive the development of effective medical countermeasures for pandemic preparedness.
CORE SERVICES:
Vaccine/Antibody Production
LEAD ORGANIZATION:
Washington University in St. Louis
Respiroviruses, Rubulaviruses, Peribunyaviruses, and Phenuiviruses present major health burdens and have pandemic potential. There are no preventative or therapeutic measures against most of the viruses in these families. By generating and analyzing large panels of monoclonal antibodies (mAbs) targeting key viral surface glycoproteins, Antibody Core D identifies protective epitopes and informs the design of next-generation vaccines. Through advanced technologies like single-cell sorting and RNA sequencing, the Core develops potent mAbs with high resistance barriers for potential therapeutic use. This work provides critical insights into antibody responses and drives the development of vaccines and therapies to protect against emerging viral threats
CORE SERVICES:
Animal Models
Correlates of Protection
LEAD ORGANIZATION:
University of Pittsburgh
Correlates Core E focuses on identifying immune responses that provide protection against prototype viruses, supporting the development of vaccines and therapies across Center Projects. By quantifying both humoral and cellular immunity in humans and animals, and assessing neutralizing antibody responses with Core D, Core E establishes critical immune correlates of protection. Leveraging advanced machine learning, the Core aims to uncover patterns that can be applied to emerging viruses within the same families or across families. This work strengthens pandemic preparedness by guiding the design of broadly effective medical countermeasures.
R2P2 Participating Organizations & Institutions
- Biotecnopolo di Siena
- Columbia University
- The University of Texas at Austin
- University of Pittsburgh
- University of Siena
- Washington University in St. Louis