Immunological Effects and Safety of Live Rotavirus Vaccination Following Antenatal Exposure to Immunomodulatory Biologic Agents: A Canadian Immunization Research Network Study

Background: People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy; however, concerns regarding potential immunosuppression in exposed infants have led to recommendations to avoid live vaccines in the first 6-12 months of life. We examined whether live rotavirus vaccine may be administered safely to biologic agent-exposed infants assessed in the Canadian Special Immunization Clinic (SIC) Network. Methods: Six SIC sites accepted referrals for infants with biologic agent exposure for rotavirus vaccination recommendations. Children with other contraindications to rotavirus vaccination or over 15 weeks of age were excluded. Clinical and laboratory evaluations were performed according to a standard clinical pathway. Children recommended for rotavirus vaccination were followed up to 8 months after series initiation for severe and serious adverse events including severe diarrhea, vomiting, and intussusception. After parental consent, de-identified data were transferred to a central database for analysis. Findings: Between May 1, 2017 and December 31, 2021, 191 eligible infants were enrolled. Infliximab was the most common biologic agent infants were exposed to (n=68, 36%), followed by adalimumab (n=49, 26%), ustekinumab (n=18, 9%), and vedolizumab (n=17, 9%). Biologic agent exposure continued into the third trimester for over 90% of infants. No clinically significant abnormalities in lymphocyte subsets, quantitative immunoglobulins, or mitogen responses were detected. Following SIC assessment, rotavirus vaccination was recommended for 187 (98%) infants. By August 19, 2022, 168 (89.8%) infants had initiated rotavirus vaccination; 150 (80%) completed the series. No serious post-immunization adverse events were reported. Interpretation: Findings from this national cohort suggest lymphocyte subsets and the safety of live rotavirus vaccination are generally not affected by in-utero exposure to biologic agents. Rotavirus vaccination may be offered routinely to infants exposed to anti-TNF agents. Funding: Public Health Agency of Canada and Canadian Institutes of Health Research through the Canadian Immunization Research Network.