1. The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.
- Author
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Schuster, Jennifer, Hamdan, Lubna, Dulek, Daniel, Kitko, Carrie, Batarseh, Einas, Haddadin, Zaid, Stewart, Laura, Stahl, Anna, Potter, Molly, Rahman, Herdi, Kalams, Spyros, Bocchini, Claire, Moulton, Elizabeth, Coffin, Susan, Ardura, Monica, Wattier, Rachel, Maron, Gabriela, Grimley, Michael, Paulsen, Grant, Harrison, Christopher, Freedman, Jason, Carpenter, Paul, Englund, Janet, Munoz, Flor, Danziger-Isakov, Lara, Spieker, Andrew, and Halasa, Natasha
- Subjects
high dose ,influenza ,pediatrics ,stem cell recipients ,vaccination ,Humans ,Child ,Child ,Preschool ,Adolescent ,Influenza Vaccines ,Influenza ,Human ,Influenza A Virus ,H3N2 Subtype ,Influenza A Virus ,H1N1 Subtype ,Vaccines ,Inactivated ,Antibody Formation ,Hematopoietic Stem Cell Transplantation ,Transplant Recipients ,Antibodies ,Viral ,Hemagglutination Inhibition Tests - Abstract
BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.
- Published
- 2024