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Clinical Trial
. 2025 Feb 4;231(1):e123-e131.
doi: 10.1093/infdis/jiae454.

Immunogenicity and Reactogenicity of High- or Standard-Dose Influenza Vaccine in a Second Consecutive Influenza Season

Hannah Bahakel  1 , Andrew J Spieker  2 , Haya Hayek  3 , Jennifer E Schuster  4 , Lubna Hamdan  1 , Daniel E Dulek  3 , Carrie L Kitko  3 , Tess Stopczynski  2 , Einas Batarseh  3 , Zaid Haddadin  3 , Laura S Stewart  3 , Anna Stahl  3 , Molly Potter  3 , Herdi Rahman  3 , Justin Amarin  3 , Spyros A Kalams  3 , Claire E Bocchini  5 , Elizabeth A Moulton  5 , Susan E Coffin  6 , Monica I Ardura  7 , Rachel L Wattier  8 , Gabriela Maron  9 , Michael Grimley  1 , Grant Paulsen  1 , Christopher J Harrison  4 , Jason Freedman  6 , Paul A Carpenter  10 , Janet A Englund  10 , Flor M Munoz  5 , Lara Danziger-Isakov  1 , Natasha Halasa  2 ; Pediatric HCT Flu Study
Collaborators, Affiliations
Clinical Trial

Immunogenicity and Reactogenicity of High- or Standard-Dose Influenza Vaccine in a Second Consecutive Influenza Season

Hannah Bahakel et al. J Infect Dis. .

Abstract

Background: Pediatric hematopoietic cell transplant (HCT) recipients are at high risk for morbidity from influenza virus infection. We demonstrated in a primary phase 2 randomized controlled trial that 2 post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given 4 weeks apart were more immunogenic than 2 doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present the immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen.

Methods: A subcohort of study participants reenrolled and had hemagglutinin inhibition titers measured at baseline and 4 weeks after each vaccine dose in year 2. We estimated geometric mean fold rise in hemagglutinin inhibition titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (comparing HD-TIV vs SD-QIV) for each antigen at each time point. We described systemic and injection site reactions.

Results: A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Postvaccine geometric mean fold rise and adjusted geometric mean ratio estimates were higher for both groups following a single influenza vaccine dose in year 2 as compared with 2 doses of the same formulation in year 1. Both groups had similar frequencies of injection site and systemic reactions.

Conclusions: A single dose of HD-TIV or SD-QIV was more immunogenic in year 2 than 2 doses of the same formulation in year 1. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a 2-dose schedule in the prior year post-HCT.

Clinical trials registration: NCT02860039 (ClinicalTrials.gov).

Keywords: high dose; influenza; pediatrics; stem cell recipients; vaccination.

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Conflict of interest statement

Potential conflicts of interest. N. B. H. received grant support from Sanofi and Quidel and a current grant from Merck. C. E. B. receives grant support from Pfizer and Merck. J. A. E. reports grant support from AstraZeneca, Merck, Pfizer, and GlaxoSmithKline (all paid to institution) and consultant fees for AbbVie, AstraZeneca, Meissa Vaccines, Moderna, Pfizer, Sanofi Pasteur, Shinogi, and Ark Biopharma. G. M. reports research support from Astellas Inc and SymBio Pharmaceuticals. C. L. K. reports payment for participation on an advisory board for Horizon Therapeutics; payment for educational lectures from Medscape, i3Health, Physicians Education Resource, and Dava Oncology; travel support for Global Summit on Hematologic Malignancies from Dava Oncology; and payment from CSL Behring for providing graft-vs-host disease adjudication for a clinical trial. M. I. A. reports institutional research grants from Miravista Diagnostics and Merck, consulting fees from Karius, travel support for meeting attendance from the Pediatric Infectious Diseases Society and the American Academy of Pediatrics, and an unpaid position on the Pediatric Infectious Diseases Society Board of Directors. C. J. H. reports grants or contracts from GlaxoSmithKline, Pfizer, Merck, and Astellas; royalties from UpToDate; payment or honoraria for educational material from Pediatric News; and nonfinancial interests in the American Board of Pediatrics. J. L. F. reports consulting fees and stock options from Massive Bio, Inc. J. E. S. reports institutional grants or contracts from the Centers for Disease Control and Prevention, National Institutes of Health, and Food and Drug Administration; personal consulting fees from the Association of Professionals in Infection Control and Epidemiology and the Association of American Medical Colleges; and honoraria for speaking engagements from the Missouri American Academy of Pediatrics. E. A. M. reports institutional grants or contracts for clinical trials of pediatric coronavirus disease vaccines and therapeutics from Pfizer. G. C. P. reports institutional grants or contracts for COVID-19 clinical trials from Pfizer and Moderna. F. M. M. reports grants or contracts paid to institution from Gilead for antiviral research and from Pfizer for vaccine research; grant support from the National Institutes of Health and the Centers for Disease Control and Prevention; and participation as a data and safety monitoring board member for, and payments to author from, Pfizer and Moderna. A. J. S. reports grant support from the National Institutes of Health. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
CONSORT diagram displaying the cohort of study repeaters. Of the 163 participants who received both doses in year 1 (n = 80 for SD-QIV and n = 83 for HD-TIV), 65 (39.9%) reenrolled for a subsequent influenza season (n = 33 for SD-QIV and n = 32 for HD-TIV). HD-TIV, high-dose trivalent influenza vaccine; SD-QIV, standard-dose quadrivalent influenza vaccine.
Figure 2.
Figure 2.
Point estimates and 95% CIs for geometric mean HAI titers at visits 1 through 4R, shown by antigen (A/H1N1, A/H3N2, B/Victoria, and B/Yamagata) and stratified by dose group (SD-QIV and HD-TIV). Note that B/Yamagata is not included in HD-TIV. HAI, hemagglutinin inhibition; HD-TIV, high-dose trivalent influenza vaccine; SD-QIV, standard-dose quadrivalent influenza vaccine.
Figure 3.
Figure 3.
Relative frequency and severity of various reactions within each vaccine group after each of the 4 doses (doses 1 and 2 in year 1; doses 1R and 2R in year 2): A, systemic reactions; B, injection site reactions. Reaction severity was graded on a scale from 1 to 3 (mild, moderate, and severe, respectively). HD-TIV, high-dose trivalent influenza vaccine; SD-QIV, standard-dose quadrivalent influenza vaccine.
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