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Clin Infect Dis
. 2023 Oct 6:ciad534.
doi: 10.1093/cid/ciad534. Online ahead of print. 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
Jennifer E Schuster 1 , Lubna Hamdan 2 , Daniel E Dulek 2 , Carrie L Kitko 2 , Einas Batarseh 2 , Zaid Haddadin 2 , Laura S Stewart 2 , Anna Stahl 2 , Molly Potter 2 , Herdi Rahman 2 , Spyros A Kalams 3 , Claire E Bocchini 4 , Elizabeth A Moulton 4 , Susan E Coffin 5 , Monica I Ardura 6 , Rachel L Wattier 7 , Gabriela Maron 8 , Michael Grimley 9 , Grant Paulsen 9 , Christopher J Harrison 10 , Jason L Freedman 5 , Paul A Carpenter 11 , Janet A Englund 11 , Flor M Munoz 4 12 , Lara Danziger-Isakov 9 , Andrew J Spieker 13 , Natasha B Halasa 2 ; Pediatric HCT Flu Study
Collaborators, Affiliations
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.
Keywords: high dose; influenza; pediatrics; stem cell recipients; vaccination.
. 2023 Oct 6:ciad534.
doi: 10.1093/cid/ciad534. Online ahead of print. 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
Jennifer E Schuster 1 , Lubna Hamdan 2 , Daniel E Dulek 2 , Carrie L Kitko 2 , Einas Batarseh 2 , Zaid Haddadin 2 , Laura S Stewart 2 , Anna Stahl 2 , Molly Potter 2 , Herdi Rahman 2 , Spyros A Kalams 3 , Claire E Bocchini 4 , Elizabeth A Moulton 4 , Susan E Coffin 5 , Monica I Ardura 6 , Rachel L Wattier 7 , Gabriela Maron 8 , Michael Grimley 9 , Grant Paulsen 9 , Christopher J Harrison 10 , Jason L Freedman 5 , Paul A Carpenter 11 , Janet A Englund 11 , Flor M Munoz 4 12 , Lara Danziger-Isakov 9 , Andrew J Spieker 13 , Natasha B Halasa 2 ; Pediatric HCT Flu Study
Collaborators, Affiliations
- PMID: 37800415
- DOI: 10.1093/cid/ciad534
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.
Keywords: high dose; influenza; pediatrics; stem cell recipients; vaccination.