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

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: >11-fold increase in geometric mean titers compared to pre-vaccination levels for H-QIV

• Primary Outcome: H-QIV demonstrated superior immunogenicity with seroprotection rates >95% and seroconversion rates >89% for all four influenza strains

• Nnt Or Sensitivity: Seroprotection rates >95% and seroconversion rates >89% for H-QIV across all strains

• Confidence Interval: Not reported in abstract

Clinical Application

High-dose formulation appears feasible with comparable safety profile to standard low-dose vaccines Relevant to Australian immunisation schedule for young children; would require TGA evaluation for registration and potential PBS listing consideration given superior immunogenicity profile Children aged 6-35 months requiring influenza vaccination, particularly those at high risk for severe influenza complications

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.

References

1. 1.Guo, X., Li, J., Dong, X., Xing, K., Xu, X., Xu, W., Wang, C., Li, K., Gao, X., Qiu, Y., Guo, Z., Xu, W., Zhao, C., Ma, Y., Wu, Y., Liu, X., & Li, G. (2026). 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. Human Vaccines & Immunotherapeutics. https://doi.org/10.1080/21645515.2026.2665017