Human papillomavirus 16/18 vaccine recombinant bivalent(Xiamen Innovax)

This study aims to compare the vaccination rates and incidence of adverse reaction rates following administration of two domestically produced human papillomavirus (HPV) vaccines in individuals aged 9-30 years,investigate the impact of distinct manufacturing processes and vaccination schedules on adverse reaction rates. From November 2023 to June 2024, the Immunization Planning Department of Liuzhou Center for Disease Control and Prevention conducted a single-center, randomized, open-label, parallel-group trial using community-based recruitment of eligible participants aged 9 to 30 years. Participants were randomly assigned to receive either of two domestically produced HPV vaccines (Walrinvax or Cecolin). As specified in the vaccine package inserts, subjects were stratified into a two-dose regimen group (aged 9-14 years) and a three-dose regimen group (aged 15-30 years). Vaccination rates were recorded, and adverse reactions within 0-30 days post-vaccination were monitored. The results showed that a total of 400 participants were enrolled. Both the full vaccination rate and the timely completion rate were significantly higher in the two-dose regimen group compared to the three-dose regimen group (Fisher's exact test, P<0.01; χ²=7.06, P<0.01). A total of 985 doses were administered. The overall adverse reaction rate was 18.78% (185/985), with local and systemic reactions occurring at 8.02% (79/985) and 10.76% (106/985), respectively. The most frequent adverse reactions were injection site pain (4.97%, 49/985) and fever (4.47%, 44/985). No grade 4 or special-interest adverse events were reported.The incidence of adverse reactions for the two domestic HPV vaccines with different production processes (at 0/6 months) was 13.96% (55/394) and 17.46% (69/395) respectively, with no statistically significant difference (χ²=1.83, P>0.05).The adverse reaction rate was significantly lower in the 9-14 years group (9.77%) compared the 15-30 years group (24.91%)(χ²=35.67,P<0.01). In conclusion, both domestic HPV vaccines demonstrated a favorable safety profile in the 9-30 years age group, with mostly mild adverse reactions. Compared to the three-dose schedule (15-30 years group), the two-dose HPV vaccination schedule (9-14 years group) significantly reduced the incidence of adverse reactions and improved vaccination compliance.

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.

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.

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.

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.

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.