Comparison of Two High-Dose Versus Two Standard-Dose Influenza Vaccines in Adult Allogeneic Hematopoietic Cell Transplant Recipients
Lora D Thomas, Einas Batarseh, Lubna Hamdan, Zaid Haddadin, Daniel Dulek, Spyros Kalams, Laura S Stewart, Anna L Stahl, Herdi Rahman, Justin Amarin, Haya Hayek, Michael Ison, Edgar T Overton, Steven A Pergam, Andrew J Spieker, Natasha Halasa, Bipin Savani, Kassim, Melissa Logue, Shari Barto, Rendie McHenry, Sajal Tanna, Laura Bezler, Patrice Al-Saden, Meredith Marshall, Donna Salzman, Ainsley Greenstein, Anisha Jackson, Sherree Wright, Mary Flowers, Mathilda Loeffelholz, Sarah Marquis, Elizabeth Nguyen,- Infectious Diseases
- Microbiology (medical)
Abstract
Background
Adult hematopoietic cell transplant (HCT) recipients are at high risk for influenza-related morbidity and mortality and have suboptimal influenza vaccine immune responses compared to healthy adults, particularly within two years of transplant.
Methods
This phase II, randomized, controlled, double-blind, multicenter trial compared two doses of high-dose trivalen (HD-TIV) to two doses of standard-dose quadrivalent (SD-QIV) influenza vaccine administered one month apart in adults 3-23 months post-allogeneic HCT. Hemagglutinin antibody inhibition (HAI) titers were measured at baseline, four weeks following each vaccine dose, and approximately six months post-second vaccination. Injection-site and systemic reactions were assessed for seven days post-vaccination. The primary immunogenicity comparison was geometric mean HAI titer (GMT) at visit 3 (4 weeks after the second dose); we used linear mixed models to estimate adjusted GMT ratios (aGMRs) comparing HD-TIV/SD-QIV for each antigen.
Results
We randomized 124 adults; 64 received SD-QIV and 60 received HD-TIV. Following the second vaccination, HD-TIV was associated with higher GMTs compared to SD-QIV for A/H3N2 (aGMR=2.09; 95%CI: [1.19, 3.68]) and B/Victoria (aGMR=1.61; 95%CI [1.00, 2.58]). The increase was not statistically significant for A/H1N1 (aGMR=1.16; 95%CI: [0.67, 2.02]). There was a trend to more injection-site reactions for HD-TIV after the second vaccination compared to SD-QIV (50% vs. 33%; aOR=4.53; 95%CI [0.71, 28.9]), while systemic reactions were similar between groups with both injections.
Conclusion
Adult allogeneic HCT recipients who received two doses of HD-TIV produced higher HAI antibody responses for A/H3N2 and B/Victoria compared with two doses of SD-QIV, with comparable injection-site or systemic reactions.