Longitudinal Meta-cohort study protocol using systems biology to identify vaccine safety biomarkers

Joann Diray-Arce; Ana C Chang; Sara Moradipoor; Donato Amodio; Bruce Carleton; Wan-Chun Chang; Nigel W Crawford; Meagan Karoly; Annmarie Hoch; Kerry McEnaney; Tahir S Kafil; Mahitha Donthireddy; Sarah K Steltz; Simon D van Haren; Asimenia Angelidou; Kinga K Smolen; Hanno Steen; Jessica Lasky-Su; Huyen Tran; Peter Liu; C Buddy Creech; Clare L Cutland; Helen Petousis-Harris; Ishac Nazy; Rae S M Yeung; Sonali Kochhar; Steve Black; Nicholas Wood; Dale Nordenberg; Paolo Palma; Inna G Ovsyannikova; Richard B Kennedy; Gregory A Poland; Al Ozonoff; Robert T Chen; Ofer Levy; Karina A Top; International Network of Special Immunization Services (INSIS) Members

doi:10.1016/j.vaccine.2025.127504

Longitudinal Meta-cohort study protocol using systems biology to identify vaccine safety biomarkers

Vaccine. 2025 Aug 30:62:127504. doi: 10.1016/j.vaccine.2025.127504. Epub 2025 Jul 26.

Authors

Joann Diray-Arce¹, Ana C Chang², Sara Moradipoor³, Donato Amodio⁴, Bruce Carleton⁵, Wan-Chun Chang⁵, Nigel W Crawford⁶, Meagan Karoly², Annmarie Hoch², Kerry McEnaney², Tahir S Kafil⁷, Mahitha Donthireddy², Sarah K Steltz², Simon D van Haren⁸, Asimenia Angelidou⁹, Kinga K Smolen⁸, Hanno Steen¹⁰, Jessica Lasky-Su¹¹, Huyen Tran¹², Peter Liu¹³, C Buddy Creech¹⁴, Clare L Cutland¹⁵, Helen Petousis-Harris¹⁶, Ishac Nazy¹⁷, Rae S M Yeung¹⁸, Sonali Kochhar¹⁹, Steve Black¹⁶, Nicholas Wood²⁰, Dale Nordenberg²¹, Paolo Palma⁴, Inna G Ovsyannikova²², Richard B Kennedy²², Gregory A Poland²², Al Ozonoff²³, Robert T Chen²⁴, Ofer Levy²³, Karina A Top²⁵; International Network of Special Immunization Services (INSIS) Members

Affiliations

¹ Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: joann.arce@childrens.harvard.edu.
² Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
³ Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada.
⁴ Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome 00165, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy.
⁵ Department of Pediatrics and BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
⁶ Murdoch Children's Research Institute (MCRI_AEFI-CAN) & University of Melbourne, Parkville, VIC 3052, Australia.
⁷ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
⁸ Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
⁹ Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
¹⁰ Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
¹¹ Harvard Medical School, Boston, MA 02115, USA; Channing Division of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹² Monash University, Melbourne, VIC 3004, Australia.
¹³ University of Ottawa Heart Institute, Ottawa, ON K1W 4W7, Canada.
¹⁴ Vaccine Research Program, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
¹⁵ African Leadership in Vaccinology Expertise (Wits-Alive), Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg 2050, South Africa.
¹⁶ Global Vaccine Data Network and School of Population Health, University of Auckland, 1142, New Zealand.
¹⁷ Department of Medicine McMaster University, Hamilton, ON L8S 4K1, Canada; Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
¹⁸ Cell and Systems Biology Research Program, The Hospital for Sick Children, Departments of Paediatrics, Immunology and Institute of Medical Sciences, University of Toronto, Toronto, ON M5G 1X8, Canada.
¹⁹ Global Healthcare Consulting, New Delhi 110024, India; University of Washington, Seattle, WA 98915, USA.
²⁰ University of Sydney, Sydney, NSW 2006, Australia.
²¹ Thriive, Bronx, NY, USA; Safety Platform for Emergency vACcines (SPEAC), Brighton Collaboration, The Task Force for Global Health, Decatur, GA 30030, USA.
²² Vaccine Research Group, Division of General Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
²³ Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
²⁴ Brighton Collaboration, Task Force for Global Health, Decatur, GA 30030, USA.
²⁵ Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada; Li Ka Shing Institute of Virology and Women's and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Departments of Community Health & Epidemiology, Dalhousie University, Halifax, NS B3H 4R2, Canada.

Abstract

The International Network of Special Immunization Services (INSIS) was established to investigate the causes and risk factors of rare adverse events following immunizations (AEFIs) and develop immunization strategies for mitigating or preventing risk for individuals with prior AEFIs or at risk of AEFIs. INSIS integrates clinical data with multi-omic technologies (e.g., transcriptomics, proteomics, metabolomics) through a global consortium of clinical networks, leading immunology, pharmacogenomics teams to uncover the molecular mechanisms behind AEFIs. The network ensures accurate and standardized data collection and analysis through rigorous data management and quality assurance processes. INSIS also implements harmonized case definitions and protocols for collecting data and samples related to rare AEFIs, such as myocarditis, pericarditis, and Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) after COVID-19 vaccinations. This protocol outlines the comprehensive approach to enhance risk-benefit assessments of vaccines across populations, identify actionable biomarkers to inform discovery and development of safe vaccines, and support personalized vaccination strategies.

Keywords: AEFI; Adverse event of following immunization; Adversomics; Biomarker discovery; COVID-19 vaccines; INSIS; Multi-omics; Myocarditis; PF4; Pericarditis; Systems biology; TTS; VITT; Vaccine safety.

MeSH terms

Biomarkers* / analysis
COVID-19 / prevention & control
COVID-19 Vaccines* / adverse effects
Humans
Longitudinal Studies
Risk Assessment
SARS-CoV-2 / immunology
Systems Biology* / methods
Vaccination* / adverse effects
Vaccines* / adverse effects

Substances

Biomarkers
COVID-19 Vaccines
Vaccines

Grants and funding

K08 AI168487/AI/NIAID NIH HHS/United States