Mount Sinai to Lead Development of Pan-Coronavirus Vaccine Under New Federal Grant
The Icahn School of Medicine at Mount Sinai has been awarded a five-year, $13 million federal grant to bring together experts from multiple disciplines across five research institutions to create better vaccines against current as well as emerging coronaviruses.
While considerable progress has been made to develop interventions to treat and prevent COVID-19, the continued emergence of viral variants with increased transmissibility and resistance to antibody neutralization highlights the urgent need for continued research into the correlates of long-lasting immune protection to design the next generation of universal coronavirus vaccines.
The Programming Long-lasting Immunity to Coronaviruses (PLUTO) project, funded by the National Institute of Allergy and Infectious Diseases (NIAID), will be led by Viviana Simon, MD, PhD at Mount Sinai and Ali Ellebedy, PhD, at Washington University School of Medicine in St. Louis.
PLUTO researchers will figure out what makes our immune response strong and long-lasting against coronaviruses. The team will then develop vaccines that offer broad protection against existing and future SARS-CoV-2 variants, as well as pandemic, zoonotic (those that can jump from animals to humans), and seasonal coronaviruses responsible for other illnesses.
“Our multidisciplinary team is poised to tackle the challenges posed by coronaviruses head on. By pooling our expertise and resources, we aim to develop next-generation coronavirus vaccines with broad protection, thus contributing significantly to curbing the current pandemic and averting future coronavirus-related public health crises.”
Viviana Simon, MD, PhD, Professor of Microbiology; Pathology, Molecular and Cell-Based Medicine; and Medicine (Infectious Diseases) at the Icahn School of Medicine at Mount Sinai
The long-term goal of PLUTO is to develop variant-proof, universal vaccines that protect against many different coronaviruses in a long-lasting manner. Such vaccines will help curb the current SARS-CoV-2 variants and reduce the risk of future pandemics associated with different coronaviruses.
To achieve its ambitious research agenda, the PLUTO program has assembled a team of investigators with extensive expertise in virology, immunology, pathogenesis, universal vaccine development, and structural biology who have a well-established track record of successful collaborations.
“The assembled team has a track record of success in designing these types of broadly protective universal vaccines, bringing universal influenza vaccine candidates into clinical development. Using the same methods and strategies, we are confident that our PLUTO efforts will result in similar successes.”
Ali Ellebedy, PhD, Associate Professor of Pathology and Immunology, Medicine and Molecular Microbiology at Washington University School of Medicine in St. Louis
To understand the interplay between an evolving viral pathogen and the host antibody responses at the cellular, molecular, and structural levels, the team will leverage an exceptional set of biological specimens. Those specimens include longitudinal blood samples from vaccinated and boosted individuals who were infected with recent SARS-CoV-2 variants such as Omicron, or seasonal coronaviruses; longitudinal samples from blood, draining lymph nodes, and bone marrow from individuals who received first-generation SARS-CoV-2 mRNA vaccines as well as those who received mRNA vaccines that are based on the recent Beta and Delta variants. This will allow for an in-depth characterization of responses by B cells, a type of specialized immune system cells.
About the PLUTO Project
Under PLUTO, two complementary research projects will establish correlates of robust, durable, and protective coronavirus humoral immunity (Project 1) and design and test efficacy of viral variant-proof pan-sarbecovirus and pan-betacoronavirus vaccines (Project 2). To support the successful completion of the research aims, several Core groups will synergize the two research projects.
The Cores will synergize with the two research projects to support the successful completion of the research aims. The Administrative Core will manage the consortium, coordinate cross-project activities, and create the structure and environment needed to accomplish PLUTO’s goals. The Antibody Core will develop large panels of recombinant monoclonal antibodies (mAbs) against coronavirus spike proteins to define specificity and breath of immune responses elicited by coronavirus infections and/or vaccinations in humans and animal models. The Animal Model Core will provide a central resource with approvals, facilities, and expertise to assess efficacy of broadly cross-reactive coronavirus antibodies and vaccines in robust pre-clinical models against a spectrum of coronaviruses, including Select Agents.
A multidisciplinary team of scientists from five institutions who have an outstanding track record of working collaboratively will conduct the proposed studies. The Research Projects will collaborate with each other and with the Antibody and Animal Model Cores, coordinated by the Administrative Core. The integrated and synergistic activities across Projects and Cores will drive the successful completion of the program project’s ambitious research agenda, enabling achievement of the long-term PLUTO goal of developing variant-proof pan-sarbecovirus and pan-betacoronavirus vaccines. These findings will contribute to curbing the current SARS-CoV-2 pandemic and mitigate the risk of future pandemics with coronaviruses.
Sources: NIH RePORT, Icahn School of Medicine