This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) provides $464,750 to the Icahn School of Medicine at Mount Sinai to investigate the mechanisms of mucosal immune responses induced by mRNA-based and Newcastle Disease Virus (NDV)-based COVID-19 vaccine platforms. The research aims to understand how these vaccine technologies can prime mucosal B cells and promote their recirculation to induce...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) provides $200,016 to The Regents of the University of California, San Francisco (UCSF) to conduct a 5-year research program focused on elucidating the mechanisms by which certain children develop critical illness from SARS-CoV-2 infection. The key objectives are to: 1) Define and characterize the autoantibody repertoire in children with severe...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) provides $380,320 to the Trustees of the University of Pennsylvania, doing business as the Clinical Practices of the University of Pennsylvania, to conduct research on elucidating the lineage dynamics of optimal human CD8 T cell responses to SARS-CoV-2 and how CD8 T cell homeostasis is altered in Long COVID. The research aims to define human memory...
This Project Grant award of $305,000.00 from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), supports research to investigate the role of stem-like T cells in multiple sclerosis (MS) disease progression. The key objectives are to: Rigorously test the hypothesis that a continuing stemness and differentiation of CD4+ T stem cells results in functional and transcriptomic diversification under evolving...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $687,422 to the Benaroya Research Institute at Virginia Mason to conduct research focused on CD4+ tissue resident memory T cells and their role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The key objectives are to: 1) characterize the diversity...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research federal grant program (CFDA 93.855), provides $286,791 to Childrens Hospital Medical Center in Cincinnati, Ohio to develop and apply pediatric-specific blood transcriptional modules (PBTMs) across diverse geographical settings through public data mining. The project aims to construct robust and widely applicable PBTMs that capture the broad range...
This federal Project Grant award of $192,888 from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) supports research to evaluate the generation, differentiation, breadth, and persistence of SARS-CoV-2-specific CD4+ and CD8+ T cell responses in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) patients after vaccination and infection. The goal is to provide in-depth knowledge of...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $193,644 to The Trustees of Columbia University in the City of New York to conduct research on the impact of immune imprinting from prior SARS-CoV-2 variant exposure on antibody responses to emerging variants. The key objectives are to: 1) Test the effect of immune imprinting on neutralizing antibody responses in a...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $563,588 to Weill Medical College of Cornell University to study the effects of immunosuppression on SARS-CoV-2 persistence, virus genetic diversity, and clinical outcomes of COVID-19. The research aims to determine the immune defects linked to prolonged SARS-CoV-2 replication in immunocompromised hosts, and...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), is supporting research to investigate the role of T cells in promoting post-acute memory deficits after COVID-19 infection in mice. The $107,995 award to The Washington University, which runs from July 2025 to June 2027, will fund a study to determine how pathogenic CD4+ T cells are recruited to the central nervous...
SEROLOGICAL AND CELLULAR IMMUNE RESPONSE TO SARS-COV-2 VACCINATION IN PEDIATRIC MULTIPLE SCLEROSIS ON IMMUNOTHERAPY - PROJECT SUMMARY/ABSTRACT MOUNTING AN EFFECTIVE ANTIBODY AND CELLULAR IMMUNE RESPONSE TO SARS-COV-2 VACCINATION IS CRITICAL FOR ITS EFFICACY TO REDUCE THE RISK OF SEVERE COMPLICATIONS AND DEATH IN COVID-19. PATIENTS WITH MULTIPLE SCLEROSIS (PWMS) ARE AT INCREASED RISK FOR SEVERE COVID-19 AND CAN HAVE ALTERED IMMUNE RESPONSES TO SARS-COV-2 VACCINATION. IN ADDITION, THE TYPE OF DISEASE-MODIFYING THERAPY (DMT) FURTHER INCREASES THE RISK FOR BREAKTHROUGH COVID-19 INFECTION AND RISK FOR SEVERE COVID-19 AND DEATH IN PWMS. FOR EXAMPLE, WHILE ANTI- CD20 MONOCLONAL ANTIBODIES (ANTI-CD20 MABS) AND SPHINGOSINE-1-PHOSPHATE RECEPTOR MODULATORS (S1PMS) BOTH DECREASE ANTIBODY RESPONSE TO SARS-COV-2 IN ADULT PWMS, THE PATIENT'S SARS-COV-2-SPECIFIC T-CELL RESPONSES ARE BLUNTED IN S1PMS BUT NOT ANTI-CD20 MABS. ALTHOUGH MUCH IS KNOWN ABOUT ADULT PWMS, LIMITED DATA IS AVAILABLE ON VACCINE RESPONSES IN PEDIATRIC-ONSET MULTIPLE SCLEROSIS (POMS) ON SIMILAR THERAPIES. VULNERABLE AND UNDERSTUDIED, CHILDREN HAVE DIFFERENT IMMUNE SYSTEMS THAN ADULTS AND CAN MOUNT DIFFERENT IMMUNE RESPONSES TO SARS-COV-2 IMMUNIZATION. HERE, WE PROPOSE INVESTIGATING HOW DIFFERENT IMMUNOTHERAPIES (ANTI-CD20 MABS VS. S1PM) AFFECT VACCINE RESPONSE IN PWMS ACROSS AGE. WE WILL USE OUR NEW MULTIPARAMETER TECHNOLOGY, FLOWBEAT, TO MEASURE THE TYPE (IGM, IGG1, IGG2, IGG3, IGG4, IGA1, IGA2, IGE) AND SPECIFICITY (22 ANTIGENS, INCLUDING STRUCTURAL AND NON-STRUCTURAL SARS-COV-2 AND HCOV PROTEINS, AND A PANEL TO DETECT AUTOANTIBODIES ASSOCIATED WITH COVID-19 SEVERITY) OF ANTIBODY RESPONSES TO SARS-COV-2 VACCINATION AND THEIR ABILITY TO NEUTRALIZE SARS-COV-2 INFECTION, ALONG WITH PSEUDOVIRUS NEUTRALIZATION ASSAYS (AIM 1). WE WILL ALSO CHARACTERIZE THE PHENOTYPE AND FUNCTION OF THE PATIENT'S SARS-COV-2-SPECIFIC B-CELL AND T-CELL SUBSETS USING HI-D FLOW AND MASS CYTOMETRY (AIM 2). CHARACTERIZING THE SARS-COV-2-SPECIFIC HUMORAL (ANTIBODIES) AND CELLULAR (MEMORY B AND T CELL) RESPONSES AFTER VACCINATION WILL DETERMINE WHETHER THE DIFFERENT IMMUNOTHERAPY REGIMENS, ANTI-CD20 MABS VS. S1PMS, CAN AFFECT THE DEVELOPMENT OF A PROTECTIVE VACCINE RESPONSE, INCLUDING ROBUST NEUTRALIZING ANTIBODIES IN PWMS ACROSS AGE. OUR PRELIMINARY DATA SUGGEST DEFICIENT IGG1 RESPONSES IN POMS ON S1PM BUT NOT ON ANTI-CD20 MABS. THUS, WE HYPOTHESIZE THAT THE IMMUNOTHERAPY TYPE (ANTI-CD20 MABS VS. S1PM) WILL PREDICT THE QUALITY OF THE MEMORY B- AND T-CELL RESPONSES, INCLUDING ALTERATIONS IN NEUTRALIZING ANTIBODIES, AND THAT THIS PROTECTIVE IMMUNE RESPONSE WILL DEPEND ON AGE. WE EXPECT THIS WORK TO INFORM THERAPEUTIC DECISIONS PRESCRIBED TO VULNERABLE MS PATIENTS AND GUIDE FUTURE VACCINE STRATEGIES TO MAXIMIZE VACCINE EFFICACY IN OTHER PATIENTS ON SIMILAR IMMUNOTHERAPIES.