Immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil9 in Chinese women aged 18–26 years: three-year follow-up data from a randomised clinical trial

Abstract

Background

Cecolin9, a second-generation 9-valent HPV vaccine derived from the WHO-prequalified Cecolin, has received marketing authorisation in China in May 2025. The non-inferiority of type-specific immune responses between Cecolin9 and Gardasil9 has been previously established at month 7 in Chinese women aged 18–26 years (NCT04782895). This study aimed to compare the plateau antibody levels between the two vaccines three years post the first dose.

Methods

This was a prospective extension study of a randomised, single-blind trial conducted in China (ClinicalTrials.gov, NCT06197802). All the participants included in the base study were invited to participate in this extension. Blood samples were collected at year 3 (median follow-up time of 34 months) for neutralising antibody detection, assessed by a triple-colour pseudovirion-based neutralisation assay. The primary outcome, geometric mean concentrations (GMCs), was analysed within three-dose recipients without major protocol violations, seronegative for the relevant type at baseline, and with available serum results at year 3. Non-inferiority of the GMC ratios (Cecolin9 vs Gardasil9) was determined as the lower bound of the two-sided 95% confidence interval (CI) in excess of 0.5.

Findings

Of the 487 participants enrolled in the base study, 82.8% (403/487) completed the three-year follow-up visit. The mean age at the first vaccination was 22.2 years among the 200 Cecolin9 recipients and 22.1 years among the 203 Gardasil9 recipients, respectively. The GMC ratios (Cecolin9 vs Gardasil9) for all nine HPV types ranged from 0.78 (95% CI 0.64–0.95) to 1.91 (95% CI 1.54–2.37), with the lower bounds of 95% CIs spanning from 0.64 to 1.54. Furthermore, sustained seropositivity rates were similar between groups, ranging from 84.7% to 100.0% in the Cecolin9 cohort and 86.2% to 100.0% in the Gardasil9 cohort. Notably, both groups presented consistent antibody decay trends over the observation period.

Interpretation

The Cecolin9 cohort demonstrated sustained non-inferior HPV type-specific plateau antibody levels compared to the Gardasil9 cohort, supporting Cecolin9's potential for enduring protection.

Funding

National Key Research and Development Plan, the National Natural Science Foundation of China, Beijing Natural Science Foundation, Fundamental Research Funds for the Central Universities, the Fieldwork Funds for graduate students of Xiamen University, and Xiamen Innovax.