Document Type
Article
Publication Date
1-25-2024
Identifier
DOI: 10.1093/cid/ciad534; PMCID: PMC10810702
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.
Journal Title
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume
78
Issue
1
First Page
217
Last Page
226
MeSH Keywords
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
Keywords
high dose; influenza; pediatrics; stem cell recipients; vaccination
Recommended Citation
Schuster JE, Hamdan L, Dulek DE, et al. 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. Clin Infect Dis. 2024;78(1):217-226. doi:10.1093/cid/ciad534
Comments
Grants and funding
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher's Link: https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciad534