Infant RSV Immunity Study (IRIS)

Understanding the Impact of Early-life RSV Infections on Infant Immunity and Long-term Health

Respiratory Syncytial Virus (RSV) is a main global cause of respiratory illness and death in infants. Previous infant vaccine trials have failed to demonstrate protection. Moreover, RSV infection during early infancy, particularly in infants younger than 4 months of age, is associated with more severe disease, reduced immune protection, and an increased risk of developing childhood asthma. This study aim to investigate the immunological and long-term health effects of a first exposure to RSV early (<4 months) versus late (>6-9 months) in infancy.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Synctial Virus; Asthma Childhood

Detailed Description

In British Columbia (Canada), RSV cases rise each year after mid-October, until April, peaking in December. This study compares outcomes between infants born in April to June, who will be naturally exposed to RSV >6-9 months of age versus infants born in September to November, who will be naturally exposed to RSV <4 months of age. Most infants become infected during their first RSV year.

Primary Objectives:

1. Compare post-season RSV immune responses between the spring cohort of infants born in April to June versus the fall cohort of infants born in September to November.
2. Compare respiratory outcomes at 3 years of age between the spring cohort of infants born in April to June versus the fall cohort of infants born in September to November.

Secondary Objectives:

1. Identify immune maturation events linked to stronger post-season RSV antibody responses.
2. Determine how the gut and upper airway microbiota co-evolve in infants over the first year of life, and how these dynamics shape RSV risk, and are shaped by host-related, and specifically seasonal factors (i.e. Apr-Jun versus Sept-Nov).
3. Compare immune responses during acute RSV infections between the spring cohort of infants born in April to June versus the fall cohort of infants born in September to November.

Design:

Prospective, observational cohort study of 300 parent-infant pairs born in the spring (April-June) or fall (Sept-Nov), with follow-up at 3 years of age.

Recruitment and Informed Consent Procedure:

Birthing parents planning to give birth at the BC Women's Hospital or live locally in greater Vancouver are identified through the BC Women's Hospital prenatal ultrasound clinic or social media and contacted by the study coordinator in person, by telephone or by text message. Interested participants complete an online eligibility questionnaire and, if eligible, the online consent form. Study advertisements posted in the hospital, local clinics, local community centers and on social media direct interested parents to the study website, online eligibility questionnaire and the study coordinators contact information.

Patients who delivered an infant during the study eligibility period in the Vancouver Coastal Health region are also invited by mail and enrolled prior to the start of the respiratory season for the spring cohort (September/October 2026) or prior to the post-season study visit for the fall cohort (May/June 2027).

Written informed consent is obtained from all participants prior to study procedures. The study has been approved by the University of British Columbia Children's and Women's Research Ethics Board (H25-02623).

Study Procedures:

At enrollment, parents are asked to complete a baseline questionnaire that collects basic pregnancy information (e.g. maternal age, pregnancy conditions, number of babies in pregnancy), intention to receive or receipt of RSV maternal vaccine, household size / number of siblings at home and their ages, smoking, family history of asthma/use of inhalers, use of antibiotics during pregnancy, family history of atopy / asthma, presence of furry pets in the home.

In each post-season questionnaire, parents are also additionally asked about socioeconomic factors, travel, daycare use, child medication use, child hospitalization or medical visit for a respiratory infection and if their child experienced asthma or wheezing symptoms. Study staff review hospital charts at birth and each year after the respiratory season to gather information about RSV-related hospitalizations and RSV testing.

Parents complete a child feeding questionnaire at 3, 6 and 12 months to collect information on infant/child dietary intake including breastfeeding and formula use (start/end dates, duration) and introduction of solid foods.

Biospecimen Collection:

A cord blood sample collected at delivery. If cord blood cannot be collected, a peripheral blood sample is taken at a scheduled study visit within one month after birth, at BC Children's Hospital. If enrolled greater than 1 month after delivery, cord/peripheral blood is not collected. To account for pre-season RSV antibody levels in the analysis, an additional pre-season dried blood spot (DBS) sample are collected in September from the spring cohort babies. We also obtain a residual sample from the Newborn Screening DBS at birth in all infants, for measurements of RSV antibody levels and neutralization titers.

A post-season blood sample is collected from all participants at a scheduled study visit at BC Children's Hospital in May or June following the RSV season.

Serology samples are used to quantify RSV antibodies and neutralization titers, and RSV F-specific antibody-dependent function.

Cord blood and peripheral blood mononuclear cells are stored from the cord and post-natal blood samples, to measure RSV T and B cell responses. A sample is also stored for whole blood RNA-Sequencing studies (PAXgene).

Prenatal and delivery serology samples are obtained from routine samples collected from birthing parents. An additional maternal blood sample is collected at the scheduled post-season study visit in May or June 2027.

RSV Testing and Respiratory Outcome Questionnaires:

Infants are monitored for respiratory outcomes (wheezing episodes) throughout each RSV season (September to March) using parent-completed diaries and parent-collected nasal swab testing when child exhibit pre-defined symptom criteria for infection (e.g. fever, cough, nasal congestion, difficulty breathing).

A subset of infants who test positive for RSV during the acute illness are invited to provide a blood sample about 2 weeks into the acute illness.

Diaries will be used for parents to record each episode of a respiratory infection, the severity and duration of the episode, and to track wheezing days.

Microbiome Studies:

A subset of at least 50 birthing parents in each (Apri-Jun / Sept/Nov) group provide a self-collected vaginal swab within 2 weeks after birth.

Oral swabs are collected from the infants around 2 weeks of age. In addition, stool samples are collected on children at 3, 6, 9 and 12 months of age. For children recruited greater than 1 month after delivery, microbiome samples are not collected.

Main Outcomes:

The study sample size is determined based on the respiratory outcome at 3 years, using the Child Healthy Infant Longitudinal Development study has developed and validated the (CHILDhood Asthma Risk Tool) CHART tool.

The main post-season outcomes are RSV antibody levels and neutralization, with main comparisons between the spring and fall groups/cohorts.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Pascal Lavoie, MDCM PhD FRCPC; Phone Number: 604-875-2135; Email: plavoie@bcchr.ca
• Study Contact Backup: Name: Allison Watts, PhD; Phone Number: 6705 604-875-2000; Email: awatts@bcchr.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Recruiting
      • BC Women's Hospital and Health Centre
      • Contact: Pascal Lavoie, MD PhD; Phone Number: 7318 (604) 875-2000; Email: plavoie@bcchr.ca
      • Contact: Allison Watts, PhD; Phone Number: 604-875-2135; Email: awatts@bcchr.ca
      • Principal Investigator: Pascal Lavoie, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Birthing parents who have a due date or delivery date in April, May or June 2026 (spring group/cohort) or September, October or November 2026 (fall group/cohort) with follow-up of the birthing parent and child during the 2026-2027, 2027-2028 and 2028-2029 RSV seasons. Children will be followed up to 3 years of age. The cohort will consist of 300 birthing parent-child pairs, with 150 in the spring cohort and 150 in the fall cohort. Birthing parents are recruited during antenatal care or shortly after delivery from the ultrasound clinic or delivery wards at BC Women's Hospital, patient lists from local maternity wards within the Vancouver Coastal Health Authority or advertisements at local prenatal care centres (obstetrician, physician and midwife clinics), community centres or on social media.

Description

Inclusion Criteria:

Birthing parent/child pairs with a delivery date in April, May or June or September, October or November who delivered or are planning to deliver at BC Women's Hospital + Health Centre or a nearby, local hospital.

Exclusion Criteria:

Severe pregnancy-related complications or chronic medical conditions in the children making them automatically eligible to receiving RSV immunoprophylaxis in British Columbia (e.g. infants born prematurely < 35 weeks of gestation, or with chronic medical conditions).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Fall group/cohort; Infants exposed to RSV <4 months of age (born September-November)
Spring group/cohort; Infants exposed to RSV >6-9 months of age (born April-June)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RSV antibody response	i) RSV neutralization titers (expressed as dilution titer to prevent 95% neutralization in vitro; NT95) ii) RSV F-specific antibody-mediated complement activation iii) RSV F-specific antibody-mediated phagocytosis	Post-respiratory season 2027 (May 2027)
Asthma symptoms	Children will be categorized as having low, moderate or high risk of asthma based on asthma-like symptoms defined using the Childhood Asthma Risk Tool (CHART)	at age 3 years old

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medically attended RSV infections	Incidence of RSV and Lower Respiratory Tract Infection hospitalizations and medically attended RSV infections	At 1 year and 3 years of age
Wheezing	Proportion of infants who develop persistent wheezing after their first RSV episode, and the number of wheezing days during season, and after each episode of RSV infection.	During first RSV season (Sept to April), and each season, up to 3 years of age (for number of wheezing days during season).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut and upper airway microbiota	Characterization of gut and upper airway microbiota, with quantification of within- (α-diversity; Shannon index) and between-sample (β-diversity; Bray-Curtis or UniFrac) diversity.	0, 3, 6, 9 and 12 months

Collaborators and Investigators

• Sponsor: University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: June 11, 2026
• First Submitted That Met QC Criteria: June 11, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: infants; cohort study; Immune response; season of birth
• Other Study ID Numbers: F25-01060

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Pending approval by our local Research Ethics Board.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No