Immune Development in Early Life (IDEaL) longitudinal cohort study protocol: Identifying biomarkers of vaccine responsiveness, respiratory infection, and asthma

doi:10.1016/j.jacig.2025.100517

. 2025 Jun 23;4(4):100517.

doi: 10.1016/j.jacig.2025.100517. eCollection 2025 Nov.

Immune Development in Early Life (IDEaL) longitudinal cohort study protocol: Identifying biomarkers of vaccine responsiveness, respiratory infection, and asthma

Donato Amodio^{1

2}, Chiara Rossetti¹, Asimenia Angelidou^{3

4

5}, Marco Sanna¹, Silvia Cellini¹, Maria Carla Marrero Cabrera¹, Martina Acciaccarelli¹, Alessia Neri^{1

6}, Giuseppe Pontrelli⁷, Marco Roversi⁶, Herbet Carmelo Carlo Valensise^{8

9}, Daniele Farsetti^{8

9}, Sanya Thomas^{3

5}, Annmarie Hoch³, Caitlin Syphurs³, Ravinder Kaur¹⁰, Kinga K Smolen^{3

5}, Simon van Haren^{3

5}, Hanno Steen^{3

5

11}, Joann Diray-Arce^{3

5}, David Martino^{12

13}, Kerry McEnaney³, Michael Pichichero¹⁰, Jessica Lasky Su^{5

14}, Ofer Levy^{3

5

15}, Paolo Palma^{1

2}; IDEaL Consortium

Collaborators, Affiliations

Collaborators

IDEaL Consortium:
Ana Chang¹⁶, Ken Kraft¹⁷, Caitlyn McLoughlin¹⁷, Al Ozonoff¹⁸, Theo J Moraes¹⁹, Elena Morrocchi²⁰, Federica Betto²⁰, Andrea Gioacchino Rotulo²¹, Marco Lecis²⁰, Nicola Cotugno²², Jing Chen²³, Meagan Karoly¹⁷, Nelly Amenyogbe²⁴, William Mohn²⁵, Rachel S Kelly²⁶, Nicole Prince²⁶, Kevin M Mendez²⁷, Casey P Shannon²⁸, Scott J Tebbutt²⁹, Nikki Schultz³⁰, Nina Kresoje³⁰, Kevin Ryff¹⁷, Guzman Sanchez-Schmitz³¹, Benoit Fatou³², Oliver Karl Otto Lindhorst³², Zainab Wurie³³

Affiliations

¹ Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
² Chair of Pediatrics, Department of Systems Medicine, Tor Vergata University, Rome, Italy.
³ Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Mass.
⁴ Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Mass.
⁵ Harvard Medical School, Boston, Mass.
⁶ PhD Program in Immunology, Molecular Medicine and Applied Biotechnology, Tor Vergata University, Rome, Italy.
⁷ Center for Clinical Research and Pediatric Drug Development, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
⁸ Department of Surgical Sciences, Tor Vergata University, Rome, Italy.
⁹ Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy.
¹⁰ Rochester General Hospital Research Institute, Rochester, NY.
¹¹ Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
¹² Wal-Yan Respiratory Research Centre, The Kids Research Institute Australia, University of Western Australia, Perth, Australia.
¹³ School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia.
¹⁴ Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
¹⁵ Broad Institute of MIT and Harvard, Cambridge, Mass.
¹⁶ Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Mass.
¹⁷ Precision Vaccines Program, Boston Children's Hospital, Boston, Mass.
¹⁸ Broad Institute of MIT and Harvard, Cambridge, Precision Vaccines Program, Boston Children's Hospital, and Harvard Medical School, Boston, Mass.
¹⁹ Program in Translational Medicine, SickKids Research Institute and Division of Respiratory Medicine, SickKids, and Departments of Paediatrics and Laboratory Medicine and Pathology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
²⁰ Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
²¹ Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
²² Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, and Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy.
²³ Precision Vaccines Program, and Research Computing, Boston Children's Hospital, Boston, Mass.
²⁴ Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
²⁵ Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
²⁶ Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
²⁷ Channing Laboratory, Brigham and Women's Hospital, Boston, Mass.
²⁸ PROOF Centre of Excellence, British Columbia, and UBC Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.
²⁹ PROOF Centre of Excezllence, British Columbia, UBC Centre for Heart Lung Innovation, St Paul's Hospital, and Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³⁰ Wal-yan Respiratory Research Centre, Telethon Kids Institute, and School of Biomedical Sciences, The University of Western Australia, Stirling Highway, Nedlands, Western Australia, Australia.
³¹ Precision Vaccines Program, Boston Children's Hospital, and Harvard Medical School, Boston, Mass.
³² Department of Pathology, Boston Children's Hospital, and Harvard Medical School, Boston, Mass.
³³ Department of Pathology, Boston Children's Hospital, Boston, Mass.

PMID: 40727648
PMCID: PMC12302638
DOI: 10.1016/j.jacig.2025.100517

Immune Development in Early Life (IDEaL) longitudinal cohort study protocol: Identifying biomarkers of vaccine responsiveness, respiratory infection, and asthma

Donato Amodio et al. J Allergy Clin Immunol Glob. 2025.

. 2025 Jun 23;4(4):100517.

doi: 10.1016/j.jacig.2025.100517. eCollection 2025 Nov.

Authors

Collaborators

IDEaL Consortium:
Ana Chang¹⁶, Ken Kraft¹⁷, Caitlyn McLoughlin¹⁷, Al Ozonoff¹⁸, Theo J Moraes¹⁹, Elena Morrocchi²⁰, Federica Betto²⁰, Andrea Gioacchino Rotulo²¹, Marco Lecis²⁰, Nicola Cotugno²², Jing Chen²³, Meagan Karoly¹⁷, Nelly Amenyogbe²⁴, William Mohn²⁵, Rachel S Kelly²⁶, Nicole Prince²⁶, Kevin M Mendez²⁷, Casey P Shannon²⁸, Scott J Tebbutt²⁹, Nikki Schultz³⁰, Nina Kresoje³⁰, Kevin Ryff¹⁷, Guzman Sanchez-Schmitz³¹, Benoit Fatou³², Oliver Karl Otto Lindhorst³², Zainab Wurie³³

Affiliations

¹ Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
² Chair of Pediatrics, Department of Systems Medicine, Tor Vergata University, Rome, Italy.
³ Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Mass.
⁴ Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Mass.
⁵ Harvard Medical School, Boston, Mass.
⁶ PhD Program in Immunology, Molecular Medicine and Applied Biotechnology, Tor Vergata University, Rome, Italy.
⁷ Center for Clinical Research and Pediatric Drug Development, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
⁸ Department of Surgical Sciences, Tor Vergata University, Rome, Italy.
⁹ Division of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy.
¹⁰ Rochester General Hospital Research Institute, Rochester, NY.
¹¹ Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Mass.
¹² Wal-Yan Respiratory Research Centre, The Kids Research Institute Australia, University of Western Australia, Perth, Australia.
¹³ School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia.
¹⁴ Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
¹⁵ Broad Institute of MIT and Harvard, Cambridge, Mass.
¹⁶ Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Mass.
¹⁷ Precision Vaccines Program, Boston Children's Hospital, Boston, Mass.
¹⁸ Broad Institute of MIT and Harvard, Cambridge, Precision Vaccines Program, Boston Children's Hospital, and Harvard Medical School, Boston, Mass.
¹⁹ Program in Translational Medicine, SickKids Research Institute and Division of Respiratory Medicine, SickKids, and Departments of Paediatrics and Laboratory Medicine and Pathology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
²⁰ Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
²¹ Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
²² Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, and Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy.
²³ Precision Vaccines Program, and Research Computing, Boston Children's Hospital, Boston, Mass.
²⁴ Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
²⁵ Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
²⁶ Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
²⁷ Channing Laboratory, Brigham and Women's Hospital, Boston, Mass.
²⁸ PROOF Centre of Excellence, British Columbia, and UBC Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.
²⁹ PROOF Centre of Excezllence, British Columbia, UBC Centre for Heart Lung Innovation, St Paul's Hospital, and Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³⁰ Wal-yan Respiratory Research Centre, Telethon Kids Institute, and School of Biomedical Sciences, The University of Western Australia, Stirling Highway, Nedlands, Western Australia, Australia.
³¹ Precision Vaccines Program, Boston Children's Hospital, and Harvard Medical School, Boston, Mass.
³² Department of Pathology, Boston Children's Hospital, and Harvard Medical School, Boston, Mass.
³³ Department of Pathology, Boston Children's Hospital, Boston, Mass.

PMID: 40727648
PMCID: PMC12302638
DOI: 10.1016/j.jacig.2025.100517

Abstract

Background: Early-life immune development is a critical factor in predicting the risk of childhood respiratory infections, asthma, and poor vaccine responses. Identifying immune endotypes that predispose children to these conditions could lead to the development of predictive biomarkers and early interventions, potentially improving long-term health outcomes. The IDEaL (Immune Development in Early Life)-Rome prospective pediatric cohort, based at Children's Hospital Bambino Gesù (Rome, Italy), is part of a National Institutes of Health/National Institute of Allergy and Infectious Diseases-supported longitudinal observational study.

Objectives: To identify molecular biomarkers associated with increased susceptibility to respiratory infections, asthma, and poor vaccine responsiveness in early childhood. The study aims to establish predictive immune profiles that could guide interventions to redirect harmful immune trajectories.

Methods: Mothers are approached during pregnancy prospectively and eligible infants are enrolled at delivery. The study includes 6 planned visits up to 5 years of age. Biosamples (blood, stool, nasal swabs, and cord blood for a subset) were collected at each visit for multiomic data (cytokines, proteomics, microbiome), alongside clinical data on vaccination, infections, and wheezing.

Results: The study included 273 participants (100% enrollment completion rate). Over 2 years, clinical and multiomic data were integrated to investigate immune trajectories related to clinical outcomes. Specific data on the outcomes will be provided in future reports as longitudinal analysis continues.

Conclusions: The IDEaL-Rome cohort study seeks to identify biomarkers predicting immune development trajectories. These findings could enable early interventions to redirect harmful immune trajectories in infancy and improve health outcomes, though further studies are required to validate biomarkers and refine predictive models for clinical application.

Keywords: Vaccine responsiveness; asthma; endotypes; immune development; multiomic profiling; respiratory infection.

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Conflict of interest statement

This study was supported by the 10.13039/100000002US National Institutes of Health 10.13039/100000060National Institute of Allergy and Infectious Diseases Immune Development in Early Life (IDEaL) award U19AI168643. This work was also partially supported by the Italian 10.13039/100009647Ministry of Health and 10.13039/100021016Istituto di Ricovero e Cura a Carattere Scientifico “Bambino Gesù” through a 5 × 1000 grant to DA and PP. Disclosure of potential conflict of interest: O. Levy is a named inventor on patents held by Boston Children’s Hospital relating to vaccine adjuvants and in vitro systems that model vaccine action, a cofounder of ARMR Sciences (formerly Ovax, Inc), and a consultant to ARMR Sciences and GlaxoSmithKline (GSK). His laboratory receives sponsored research support from GSK. J.L. Su is a named inventor on patents held by Brigham and Women’s Hospital related to Aging Biomarkers. The rest of the authors declare that they have no relevant conflicts of interest.

Figures

**Fig 1**
IDEaL program cohorts. The figure displays the 5 cohorts that make up the IDEaL program: the prospective cohort at OPBG in Rome; the Expanded Program for Immunization Consortium—Human Immunology Project Consortium (EPIC-HIPC) infant cohort recruited in The Gambia and Papua New Guinea (2017-2022, NCT03246230); the Vitamin D Antenatal Asthma Reduction Trial (VDAART) cohort of pregnant persons and their offspring in 3 US-based sites (2009-ongoing follow up); the pediatric Rochester Combined Cohort (RCC) in New York state (2006-2011); and the Canadian Healthy Infant Longitudinal Development (CHILD) pediatric cohort.

**Fig 2**
Visit schedule and study procedures for the IDEaL-Rome prospective cohort. The figure illustrates the scheduled visit timeline for the IDEaL-Rome prospective cohort, along with the key procedures and analyses conducted at each visit. ∗V6 will require additional funding. *DOB*, Date of birth.

**Fig 3**
Study visits of all IDEaL program cohorts. Specific time points scheduled for other cohorts in the IDEaL program, along with the number of participants per study and the status of each study.

**Fig 4**
Recruitment strategy for IDEaL-Rome Prospective cohort.

See this image and copyright information in PMC

References

1. Zhang D., Zheng J. The burden of childhood asthma by age group, 1990-2019: a systematic analysis of Global Burden of Disease 2019 Data. Front Pediatr. 2022;10 - PMC - PubMed
1. Toivonen L., Karppinen S., Schuez-Havupalo L., Teros-Jaakkola T., Vuononvirta J., Mertsola J., et al. Burden of recurrent respiratory tract infections in children: a prospective cohort study. Pediatr Infect Dis J. 2016;35:e362–e369. - PubMed
1. Pichichero M.E., Casey J.R., Almudevar A., Basha S., Surendran N., Kaur R., et al. Functional immune cell differences associated with low vaccine responses in infants. J Infect Dis. 2016;213:2014–2019. - PMC - PubMed
1. Surendran N., Nicolosi T., Pichichero M. Infants with low vaccine antibody responses have altered innate cytokine response. Vaccine. 2016;34:5700–5703. - PMC - PubMed
1. Pichichero M.E., Casey J.R., Almudevar A. Nonprotective responses to pediatric vaccines occur in children who are otitis prone. Pediatr Infect Dis J. 2013;32:1163–1168. - PMC - PubMed

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[1] Zhang D., Zheng J. The burden of childhood asthma by age group, 1990-2019: a systematic analysis of Global Burden of Disease 2019 Data. Front Pediatr. 2022;10 - PMC - PubMed

[2] Zhang D., Zheng J. The burden of childhood asthma by age group, 1990-2019: a systematic analysis of Global Burden of Disease 2019 Data. Front Pediatr. 2022;10 - PMC - PubMed

[3] Toivonen L., Karppinen S., Schuez-Havupalo L., Teros-Jaakkola T., Vuononvirta J., Mertsola J., et al. Burden of recurrent respiratory tract infections in children: a prospective cohort study. Pediatr Infect Dis J. 2016;35:e362–e369. - PubMed

[4] Toivonen L., Karppinen S., Schuez-Havupalo L., Teros-Jaakkola T., Vuononvirta J., Mertsola J., et al. Burden of recurrent respiratory tract infections in children: a prospective cohort study. Pediatr Infect Dis J. 2016;35:e362–e369. - PubMed

[5] Pichichero M.E., Casey J.R., Almudevar A., Basha S., Surendran N., Kaur R., et al. Functional immune cell differences associated with low vaccine responses in infants. J Infect Dis. 2016;213:2014–2019. - PMC - PubMed

[6] Pichichero M.E., Casey J.R., Almudevar A., Basha S., Surendran N., Kaur R., et al. Functional immune cell differences associated with low vaccine responses in infants. J Infect Dis. 2016;213:2014–2019. - PMC - PubMed

[7] Surendran N., Nicolosi T., Pichichero M. Infants with low vaccine antibody responses have altered innate cytokine response. Vaccine. 2016;34:5700–5703. - PMC - PubMed

[8] Surendran N., Nicolosi T., Pichichero M. Infants with low vaccine antibody responses have altered innate cytokine response. Vaccine. 2016;34:5700–5703. - PMC - PubMed

[9] Pichichero M.E., Casey J.R., Almudevar A. Nonprotective responses to pediatric vaccines occur in children who are otitis prone. Pediatr Infect Dis J. 2013;32:1163–1168. - PMC - PubMed

[10] Pichichero M.E., Casey J.R., Almudevar A. Nonprotective responses to pediatric vaccines occur in children who are otitis prone. Pediatr Infect Dis J. 2013;32:1163–1168. - PMC - PubMed

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Immune Development in Early Life (IDEaL) longitudinal cohort study protocol: Identifying biomarkers of vaccine responsiveness, respiratory infection, and asthma

Collaborators

Affiliations

Immune Development in Early Life (IDEaL) longitudinal cohort study protocol: Identifying biomarkers of vaccine responsiveness, respiratory infection, and asthma

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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Abstract

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