Safety and Immunogenicity of First Russian Quadrivalent (Recombinant, Adsorbed) Human Papillomavirus (Types 6, 11, 16, 18) Vaccine in Children Aged 9–17 Years: Multicenter, Randomized, Double-Blind, Phase III Clinical Trial

Abstract

Background . Human papillomavirus (HPV) infection is a significant risk factor for the development of HPV-associated precancerous and malignant diseases. Recombinant adsorbed vaccine against HPV (types 6, 11, 16, and 18) has been developed in Russian Federation to prevent these conditions. Vaccine immunogenicity and safety have been studied in adults. Objective . The aim of the study is to evaluate the safety and immunogenicity of Russian recombinant adsorbed quadrivalent vaccine against HPV (types 6, 11, 16, and 18) in children aged 9–17 years in comparison to reference quadrivalent vaccine. Study design . Multicenter, randomized, double-blind, parallel-group, phase III clinical trial with a 1 : 1 participant allocation ratio. Methods . The study included healthy seronegative children aged 9–17 years. Study participants aged 9–13 years received either the investigational vaccine or the reference vaccine. Vaccine safety was assessed from April 2, 2024 to April 14, 2025, in all participants who received at least one vaccine dose (as-treated population). Any post-vaccination reactions and adverse events (AE) were recorded, their correlations with vaccination, severity, and duration were evaluated. The primary efficacy endpoint was the geometric mean titer ratio (GMT Ratio) of antibodies to HPV 1 month after full vaccination course (Per-Protocol (PP) population); additionally, the GMT Ratio was evaluated for every HPV type. Randomization was centralized and based on computer-generated list. Allocation concealment was ensured via the method of sequentially numbered, opaque, sealed envelopes. Results . A total of 705 AEs were registered during the study period, 426 of which were considered related to vaccination. No severe vaccination-related AEs were reported. The investigational vaccine demonstrated comparable immunogenicity to the reference drug across all four HPV types in both age cohorts. The seroconversion rate in PP population ranged from 97% to 100%. Higher GMT values were observed in participants aged 9–13 years compared to those aged 14–17 years. GMT values were higher in the investigational drug group in both age cohorts for HPV type 18. Conclusion . Favorable safety profile and adequate immunogenicity of the investigational vaccine were recorded compared to the reference vaccine in children aged 9–17 years. The obtained data suggest that the investigational vaccine is a promising drug for HPV-associated diseases prevention.