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Principal Investigator: Anne Moscona
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $44,108,652
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY.
The Vaccines and Therapeutic Antibodies to Respirovirus, Rubulavirus, Peribunyavirus and
Phenuivirus (R2P2) ReVAMPP Center will utilize both well-defined and novel approaches to develop
prototype vaccines and human monoclonal antibody (mAb)-based treatments for rapid response to viruses
from the Paramyxoviridae, Peribunyaviridae and Phleboviridae families. R2P2 is composed of four primary
Research Projects: two that collectively focus on prototype viruses of the Paramyxoviridae family including
human parainfluenza viruses 3 and 1 (HPIV3, HPIV1), and human and bat mumps virus (MuV, BatMuV); and
two that focus on prototype viruses of the Bunyavirales order including the Peribunyaviridae Oropouche (OROV)
and La Crosse (LACV) and the Phenuiviridae Rift Valley Fever virus (RVFV) and Toscana virus (TOSV). Each
project in R2P2 follows a parallel structure and makes use of the principles of reverse vaccinology, where insights
from the structural and function studies will provide a framework to understand the molecular correlates of
immunity and antigenicity and provide a roadmap for designing optimized immunogens. The foundational studies
carried out in this ReVAMPP center will fill gaps in basic understanding of viral entry and will also inform how to
extend the stabilization approaches successfully used to advance vaccines against agents with Class I fusogens
(e.g., RSV), to those with Class II. A key R2P2 feature is that all four projects compare the same three vaccine
platforms: protein subunit, mRNA, and chimeric VSV, allowing for cross comparisons that will rapidly yield
information about platform performance in translating to related pathogens. The questions of which antigen
stabilization paradigms, and which vaccine platforms are most amenable to generalizing from the prototype
pathogens will be answered in depth and breadth by these comparisons across virus families. We assembled a
collaborative team of world-renowned experts on viral envelope protein structure and function, leading
immunologists, vaccinologists with extensive experience in industry and regulatory issues, and industry partners
(e.g., Modena, GSK). The inclusion of junior investigators with exceptional promise is designed to ensure the
engagement of the next generation of leaders in viral glycoprotein biology, viral immunology and vaccinology in
pandemic preparedness. These Projects are served by an Administrative Core (Core A), a Data Management
Core (Core B), and three Scientific Cores that perform structural biology, biophysics and protein engineering
(Core C), antibody isolation and assessment (Core D), and correlates of immune protection (Core E) experiments
in collaboration with multiple projects. The knowledge accumulated in this project and the robustness of the
approaches implemented to develop prototype vaccines will be expanded to different viruses of the same families
to evaluate their potential and broad applicability against emerging viruses of the Bunyavirales order and
Paramyxoviridae family.
Terms: <Amino Acid Sequence><Animal Disease Models><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Therapy><Antigens><Assay><Bats><Binding><Bioassay><Biological Assay><Biology><Biophysics><Bunyavirales><Cell Body><Cell Mediated Immunology><Cell-Mediated Immunity><Cells><Cellular Immunity><Characteristics><Chiroptera><Clinical Treatment Moab><Collaborations><Development><Disease><Disorder><Ensure><Envelope Protein><Epidemic Parotitis><Epidemic Parotitis Virus><Evaluation><Family><Genetic><Glycoproteins><Goals><HPIV1><HPIV3><Hand><Hemadsorption Type 2 Virus><Hemadsorption Virus 1><Hemadsorption Virus 2><History><Hu-mABs><Human><Human Parainfluenza Virus 1><Human Parainfluenza Virus 3><Immune><Immunes><Immunity><Immunologist><Immunology><Industry><Infection><Investigators><Knowledge><La Crosse encephalitis virus><La Crosse virus><LaCrosse encephalitis virus><LaCrosse virus><Leadership><MAb Therapeutics><Measures><Membrane Fusion><Messenger RNA><Mice><Mice Mammals><Modern Man><Molecular><Molecular Interaction><Monoclonal Antibodies><Mumps><Mumps virus><Murine><Mus><Myxovirus parotitidis><Nature><Non-Polyadenylated RNA><Oropouche><Oropouche virus><PBMC><Para-Influenza Virus Type 1><Para-Influenza Virus Type 3><Paramyxoviridae><Paramyxovirus><Pathway interactions><Performance><Peripheral Blood Mononuclear Cell><Primary Protein Structure><Process><Productivity><Protein Engineering><Protein Subunits><Proteins><R-Series Research Projects><R01 Mechanism><R01 Program><RNA><RNA Gene Products><Receptor Protein><Recombinant Proteins><Recombinants><Recording of previous events><Research Grants><Research Personnel><Research Project Grants><Research Projects><Researchers><Resistance><Respirovirus><Ribonucleic Acid><Rift Valley Fever><Rift Valley fever virus><Rubulavirus><Site><Structure><TOSV><Testing><Therapeutic><Therapeutic Monoclonal Antibodies><Therapeutic antibodies><Toscana virus><Translating><VSV><Vaccines><Vesicular Stomatitis Virus><Vesicular stomatitis Indiana virus><Viral><Viral Activity><Viral Diseases><Viral Envelope Proteins><Viral Function><Viral Physiology><Virus><Virus Diseases><Work><antibody based therapies><antibody treatment><antibody-based therapeutics><antibody-based treatment><biophysical analysis><biophysical foundation><biophysical principles><biophysical sciences><biophysical studies><data management><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><efficacy testing><emergent virus><emerging virus><env Antigens><env Gene Products><env Polyproteins><env Protein><epidemic parotiditis><experience><experiment><experimental research><experimental study><experiments><genetic protein engineering><hands><histories><humAbs><human mAbs><human monoclonal antibodies><human monoclonals><immunogen><in vivo><industrial partnership><industry partner><industry partnership><information gathering><insight><mAbs><mRNA><model of animal><monoclonal Abs><monoclonal antibody drugs><new approaches><next generation><novel approaches><novel strategies><novel strategy><pandemic disease preparedness><pandemic planning><pandemic preparedness><pandemic readiness><parainfluenza virus><parainfluenza virus type 1><parainfluenza virus type 3><pathogen><pathway><plasmid vaccine><prophylactic><protein design><protein function><protein sequence><protein structure><protein structures><proteins structure><prototype><receptor><receptor binding><receptor bound><resistant><response><structural biology><technology platform><technology system><therapeutic mAbs><therapeutic vaccine><treatment vaccines><vaccine antibodies><vaccine candidate><vaccine development><vaccine for the treatment><vaccine for treatment><vaccine induced antibodies><vaccine platform><vaccine-induced antibodies><vaccinology><vector><vector vaccine><viral emergence><viral infection><virus infection><virus-induced disease>