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IRB No. 20-084-2 (Dr. Zhichao Fan, PI): Mechanisms and Roles of Integrin Activation of Human Blood Leukocytes

Background, Rationale and Significance: Integrins are key mediators of the recruitment of leukocytes which play critical roles in human immunity and inflammatory diseases. Insights about Integrin function hold out the prospect improved inflammatory disease prevention. Blood leukocytes including neutrophils, monocytes, and lymphocytes, all have a recruitment cascade during inflammation and infections. They can first roll on the vascular endothelium, firmly adhere (arrest) on the vascular endothelium, spread on the vascular endothelium, perform intravascular crawling, transmigrate through vascular endothelium, and finally, migrate to the site of inflammation or infections. This cascade is essential for the recruitment and immunological function of leukocytes and involved in many infectious and inflammatory diseases. Integrins, are a group of adhesion molecules vital for the recruitment cascade. Studying the mechanisms and roles of integrin activation will bring new insights into leukocyte recruitment and immune functions and invite discovery of novel treatments for infectious and inflammatory diseases. (See Protocol-Appendix for Leukocyte Recruitment, Integrin Activation Pathways and Super Resolution/ Flow Imaging Graphics- pg.10-16) This protocol is used to develop a continuing supply of fresh blood donations for the Integrin Research Laboratories under the direction of the PI @ UConn Health, Dept of Immunology where the PI recently joined. 2 recent PI authored publications are included for reviewer, explanatory of the Integrin research for which materials are to be utilized in ongoing experiments.

IRB No. 10-273S-2 (Dr. Robert Clark, PI): The Role of Unique Lipids Derived From Common Human Bacteria in Multiple Sclerosis

Study description not available

IRB No. 21-149J-1 (Dr. George Kuchel, PI): High-resolution single cell profiling of SARS-CoV-2 vaccine responsiveness in healthy adults

This study is a collaboration between The Jackson Laboratory for Genomic Medicine (JAX) in Farmington, CT and UConn Health in Farmington, CT. All recruitment, enrollment, clinical data, and sample collection will occur at the UConn Center on Aging (COA) or at the Clinical Research Center (CRC), under the direction of Dr. George Kuchel, Professor of Medicine and Director of the UConn COA. This prospective, single-site, multi-cohort observational study is designed to determine how vaccine formulations and subject age affect immunologic responses to SARS-CoV-2 vaccine and to uncover the molecular signatures (genomics) elicited by novel COVID-19 vaccines. Up to 114 SARS-CoV-2 naïve healthy men and women aged 21 years or over, from all races and ethnic backgrounds that receive the Pfizer/Moderna/J&J COVID-19 vaccine will be enrolled to this study over a one-year period. Participation will involve nine (9) study visits for adults receiving the two-dose Pfizer or Moderna vaccine and seven (7) study visits for adults receiving the single-dose J&J vaccine. Blood samples (at all 9/7 visits) and nasal swabs (at three visits) will be collected.

IRB No. 22-179J-1 (Dr. George Kuchel, PI): A deep longitudinal analysis of next generation influenza vaccines in older adults

This study is a collaboration between The Jackson Laboratory for Genomic Medicine (JAX) in Farmington, CT and UConn Health in Farmington, CT. All recruitment, enrollment, clinical data, and sample collection will occur at the UConn Center on Aging (COA), at UConn Health in Farmington, CT under the direction of Dr. George Kuchel, Professor of Medicine and Director of the UConn COA. Coded samples collected at Visits 1-17 will be securely transported to the Jackson Laboratory for Genomic Medicine (JAX), located on the UConn Health campus, for processing, storage, sequencing, and analysis. Dr. Duygu Ucar will oversee sample management and sample and data analysis per protocol. In this study, a total of sixty (60) healthy adults aged 65 years and older who have had no history of confirmed COVID-19 and have not received influenza vaccination for the approaching influenza season will be enrolled in the study and vaccinated with influenza vaccines approved by the U.S Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for individuals ≥65 years. All participants receive influenza vaccine during the 2022-23, 2023-24, and 2024-25 influenza seasons. Participants will receive Fluzone® Quadrivalent High-Dose vaccine during the 2022-23 and 2024-25 flu seasons and FLUAD® Quadrivalent during the 2023-24 flu season. Blood samples will be collected from the participants at each of the seventeen study visits over three years. Nasal swab and stool samples will also be collected from participants at 7 time-points across the study period. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this proposed study. By performing comprehensive profiling of their blood antibodies and immune cells over time, we will be able to associate specific age-related immune alterations with vaccine responder or non-responder status, thus allowing us to pinpoint biological pathways that can be targeted to enhance vaccine efficacy and that can also help us to progress towards developing a universal influenza vaccine.