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Hum Vaccin Immunother . Comparison of safety and immunogenicity between high-dose and low-dose quadrivalent influenza vaccines in children aged 6-35

tetano

Editor, Senior Moderator
Hum Vaccin Immunother


. 2026 Dec;22(1):2665017.
doi: 10.1080/21645515.2026.2665017. Epub 2026 May 27.
Comparison of safety and immunogenicity between high-dose and low-dose quadrivalent influenza vaccines in children aged 6-35 months in China: A randomized, double-blind clinical study

Xue Guo[SUP] 1 2 [/SUP], Jingyu Li[SUP] 3 [/SUP], Xufeng Dong[SUP] 4 [/SUP], Kunpeng Xing[SUP] 1 2 [/SUP], Xiaoteng Xu[SUP] 1 [/SUP], Wen Xu[SUP] 1 [/SUP], Cangning Wang[SUP] 3 [/SUP], Kexin Li[SUP] 1 [/SUP], Xuefen Gao[SUP] 4 [/SUP], Ye Qiu[SUP] 1 2 [/SUP], Zhanlong Guo[SUP] 1 [/SUP], Weijiao Xu[SUP] 1 [/SUP], Chenyan Zhao[SUP] 5 [/SUP], Yuanjia Ma[SUP] 6 [/SUP], Yehong Wu[SUP] 1 2 [/SUP], Xiaoqiang Liu[SUP] 3 7 [/SUP], Guohua Li[SUP] 4 [/SUP]


Affiliations
Abstract

Influenza vaccines for children aged 6-35 months are typically low-dose (0.25 mL, 7.5 μg hemagglutinin per strain). However, studies have shown that high-dose influenza vaccines (0.5 mL, 15 μg hemagglutinin per strain) can enhance protective efficacy without increasing the risk of adverse reactions. We conducted a randomized, double-blind clinical study in children aged 6-35 months in China. A total of 3,000 participants were randomized (1:1:1) to receive two doses of either an investigational high-dose quadrivalent influenza vaccine (H-QIV), an investigational low-dose quadrivalent influenza vaccine (LQIV-01) or a commercially available low-dose quadrivalent influenza vaccine (LQIV-02). Hemagglutination inhibition (HI) antibody titers 30 d post-vaccination were measured and vaccine safety and tolerability within 6 months post-vaccination were evaluated in these participants. The primary objectives were to demonstrate the non-inferiority of investigational vaccines to the commercially available vaccine in immunogenicity and to compare the H-QIV to L-QIVs. Both investigational vaccines demonstrated non-inferiority, with their seroprotection rates (SPRs), seroconversion rates (SCRs) and geometric mean titers (GMTs) meeting immunogenicity criteria. The H-QIV exhibited >11-fold increases in GMTs against H1N1, H3N2, B/Yamagata and B/Victoria strains compared to pre-vaccination levels, with SPRs exceeding 95% and SCRs exceeding 89%. The H-QIV was superior to both L-QIVs as it induced a stronger immune response to influenza viruses. All vaccines showed comparable safety profiles. The H-QIV can provide greater protection and benefits to this high-risk population.

Keywords: Quadrivalent influenza vaccine; aged 6–35 months; clinical trials; immunogenicity; safety.

 
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