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

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.

PMID: 40716144
DOI: 10.1016/j.vaccine.2025.127504

Free article

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

Joann Diray-Arce et al. Vaccine. 2025.

Free article

. 2025 Aug 30:62:127504.

doi: 10.1016/j.vaccine.2025.127504. Epub 2025 Jul 26.

Authors

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.

PMID: 40716144
DOI: 10.1016/j.vaccine.2025.127504

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.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KAT reports grants from the Canadian Institutes of Health Research and Public Health Agency of Canada for safety evaluation of COVID-19 vaccines outside the submitted work. OL is a named inventor on patents relating to adjuvants and human in vitro systems that predict vaccine safety assessments and reports grants for the Precision Vaccines Program from the Boston Children's Hospital Department of Pediatrics and consulting fees from Hillevax. OL and SvH are a named inventors on patents held by Boston Children's Hospital relating to vaccine adjuvants and human in vitro systems that predict vaccine safety and efficacy. JD-A reports consulting fees to Immune System Sciences. JLS is a scientific advisor to Precion Inc. and TruDiagnostic. JLS is a named inventor on patents held by Brigham and Women's Hospital related to Aging Biomarkers. OL is a co-founder of and advisor to ARMR Sciences. CBC reports grants and contracts from the NIH and CDC for vaccine clinical trials including NIH Vaccine and Treatment Evaluation Unit (including the Moderna COVE study, Janssen ENSEMBLE study, Moderna KidCOVE study) and CDC Clinical Immunization Safety Assessment Network; grants from Merck; royalties for contributions to the UpToDate program; multiple small honoraria for lectures on COVID-19 vaccines and other vaccines; consultation fees from Altimmune (COVID-19 vaccine development), Janssen (respiratory syncytial virus vaccine development), Astellas (clinical trial data and safety monitoring board), GSK (DSMB), Horizon Pharma (consultation related to care of children with chronic granulomatous disease), and Vir (influenza monoclonal antibody development); payment for expert testimony from multiple legal firms for general medical malpractice; US patent 10,981,979 B2; and serving as the president of the Pediatric Infectious Diseases Society. IN reports funding from the Public Health Agency of Canada (PHAC) and the Heart and Stroke Foundation of Canada (HSFC#G-23-0035035). HT has received research grant funding from AZ (unrelated to COVID-19 vaccination). PL and TSK report grant from the Canadian Institutes of Health Research. CLC reports a grant from GAVI, the Vaccine Alliance, for vaccine safety surveillance and serving as a member of the Brighton Collaboration Scientific committee and the Institutional Biosafety committee. GAP reports consulting fees from AstraZeneca UK Ltd., Eli Lily and Company, Emergent BioSolutions, Exelixis Inc., ExpertConnect, Genevant Sciences, Inc., GlaxoSmithKline, Janssen Global Services, LLC, Janssen Research & Development, LLC, Medicago USA, Merck, Regeneron Pharmaceuticals Inc., Sanofi Pasteur SA, Syneos Health, and Vyriad; and participation on a data safety monitoring or advisory board for AstraZeneca UK Ltd., Bavarian Nordic A/S, Dynavax Technologies, Genentech, Inc., Merck, GlaxoSmithKline, Janssen Global Services, LLC, and Janssen Pharmaceuticals, Inc. NC reports a Medical Research Future Fund grant and serving on a government advisory committee for the Australian Technical Advisory Group on Immunization-ATAGI. GAP, RBK, and IGO have received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. RBK offers consultative advice on vaccine development to Merck & Co. and Sanofi Pasteur. BC reports a CDC grant and serving as a past board member for the Rare Disease Foundation. RTC reports grants from the Coalition for Epidemic Preparedness and Innovation and the CDC; travel support from Elsevier; honoraria payments from the Brighton Collaboration; serving as the scientific director at the Brighton Collaboration; and serving as a co‑lead on the COVAX Vaccine Safety Working Group. All remaining authors: No reported conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. INSIS Members who contributed to this publication are: Baylor College of Medicine, Molecular Virology and Microbiology, Houston, TX, 77030, USA: Jennifer Whitaker, Kristen Sexson. Boston Children's Hospital, Boston, MA, 02115, USA: Al Ozonoff, Asimenia Angelidou, Ana C Chang, Annmarie Hoch, Caitlin Syphurs, Caitlyn McLoughlin, Kerry McEnaney, Hanno Steen, Jing Chen, Kinga K. Smolen, Mahitha Donthireddy, Sarah K Steltz, Simon van Haren, Joann Diray-Arce, Ofer Levy. Brighton Collaboration, Task Force for Global Health, Decatur, GA 30030, USA: Dale Nordenberg, Robert T. Chen. Channing Division of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA: Jessica Lasky-Su. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA: Tahir S. Kafil. Global Vaccine Data Network, Auckland, 1142, New Zealand: Helen Petousis-Harris, Steve Black. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 20912, USA: Kawsar Talaat. KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya, South Africa: Eunice Wangeci Kagucia, Samuel Sang. Massachusetts General Research Institute, Boston, MA, 02114, USA: Lael Yonker. McMaster University, Hamilton, ON, L8S 4 K1, Canada: Donald Arnold, Ishac Nazy,Meera Karunakaran, Rumi Clare. Monash University and Alfred Health, Melbourne, VIC, 3004, Australia: Huyen Tran. Murdoch Children's Research Institute (MCRI_AEFI-CAN), Melbourne, VIC, 3052, Australia: Annette Alafaci, Jim Buttery, Nigel Crawford. Odense University Hospital, Odense, 5000, Denmark: Lennart Friis-Hansen. Research Laboratories, Bambino Gesù Children's Research Hospital, IRCCS, Rome, 00165, Italy: Donato Amodio, Emma Concetta Manno, Paolo Palma, Veronica Santilli. Thriive, Bronx, NY: Ariel Zadok, Dale Nordenberg. The Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1 × 8, Canada: Amy Xu, Olivia Garisto, Aaron Mulivor, Ashish Nambiar, Trang Duong, Rae S. M. Yeung. Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA: Renata Engler. University Medical Center Utrecht, Utrecht, 3584, Netherlands: Fariba Ahmadizar, Sima Mohammadi. University of Alberta, Edmonton, AB, T6G 1C9, Canada: Amanda Wilson, Sara Moradipoor, Gavin Oudit, Karina A. Top. University of Auckland, 1142, New Zealand: Helen Petousis-Harris. University of British Columbia, Vancouver, BC, V6T 1Z4, Canada: Wan-Chun Chang, Bruce Carleton. University of Ottawa Heart Institute, Ottawa, ON, K1W 4 W7, Canada: Ermina Moga, Kimberly Kidder, Liyong Zhang, Peter Liu. University of Sydney, Sydney, NSW, 2006, Australia: Nicholas Wood, Vivien Chen. University of Washington, Seattle, WA, 98915, USA and Global Healthcare Consulting: Sonali Kochhar. UT Southwestern Medical Center, Dallas, TX, 75390, USA: Ann Marie Navar. Vaccine Research Group, Mayo Clinic, Rochester, MN, 55905, USA: Richard B. Kennedy, Inna G. Ovsyannikova, Gregory A. Poland. Vanderbilt University Medical Center, Nashville, TN, 37232, USA: Emily Mitchell, Kathryn Edwards, Sandra Yoder, Shelly McGehee, C. Buddy Creech. Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA: Jay Montgomery. Weill Cornell Medical College - Pediatrics, New York, NY, 10065, USA: James B Bussel. University of the Witwatersrand, Vaccines and Infectious Diseases Analytics (VIDA) Research Unit, Johannesburg, 2050, South Africa: Kimberley Gutu, Ziyaad Dangor, Clare L. Cutland.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous