The National Institute of Allergy and Infectious Diseases has awarded the Icahn School of Medicine at Mount Sinai a five-year, $13 million grant to bring together experts from multiple disciplines across five research institutions to create better vaccines against current as well as emerging coronaviruses.
The COVID-19 pandemic, caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has infected 280 million people and caused more than five million deaths worldwide since late 2019. While considerable progress has been made to develop interventions (i.e., monoclonal antibodies, antivirals, vaccines) 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 pan-coronavirus (universal coronavirus) vaccines.
The “Programming Long-lasting Immunity to Coronaviruses” (PLUTO) project will be led by 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, and Ali Ellebedy, PhD, Associate Professor of Pathology and Immunology, Medicine and Molecular Microbiology 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,” said Dr. Simon. “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.”
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.
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.
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.
“Outbreaks of emerging and re-emerging viral pathogens will continue to threaten world health, but the PLUTO program project will lead to solutions to minimize waning immunity and prevent decreased protection against these threats,” said Dr. Simon.
“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,” adds Dr. Ellebedy.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties.