Immunogenicity and safety of an Escherichia coli-produced 9-valent human papillomavirus vaccine (types 6/11/16/18/31/33/45/52/58) in healthy Chinese women aged 20-45 years: a single-center, randomized, observer-blinded, positive controlled phase 2 clinical trial

Mingwei Wei^1,2,3Hongyan Liu¹Hongyang Yu⁴Hongxing Pan^2,3Hong Tao^2,3Jing Zhang⁵Weiwei Han¹Dan Wu^1*Wenjuan Wang^2,3*Jingxin Li^1,2,3*

• ¹School of Public Health, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, China
• ²Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, China
• ³Jiangsu Provincial Medical Innovation Center, National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Nanjing, China
• ⁴Beijing Health Guard Biotechnology Inc, Beijing, China
• ⁵Sheyang City Center for Disease Control and Prevention, Yancheng, China

Background: Vaccination with prophylactic human papillomavirus (HPV) vaccines is one of the most effective measures for preventing cervical cancer and other related diseases. Here, we aimed to evaluate the immunogenicity and safety of an Escherichia coli-produced 9-valent human papillomavirus (9vHPV) vaccine. Method: We did a single-center, randomized, observer-blinded, positive controlled phase 2 clinical trial in healthy women aged 20-45 years. All eligible participants were randomly assigned (1:1:1) to receive 270ug 9vHPV, 360ug 9vHPV or the control vaccine (Gardasil) with a 0-2-6-month schedule. Serum samples were collected at day 0 and month 7 to assess IgG and neutralizing antibodies (nAbs). For HPV6/11/16/18, non-inferiority was identified for the lower limit of the 95% CI of the geometric mean titer (GMT) ratio at a margin of 0.5 and a seroconversion rate (SCR) difference at a margin of -5%. For HPV31/33/45/52/58, superiority was demonstrated if the lower limit of the 95% CI for GMT ratio is greater than 1. Results: 780 participants aged 20-45 years were enrolled, among whom 770 completed three-dose immunization schedule. The incidences of ARs within 7 days in the 270μg, 360μg and positive control groups were 38.85%, 41.92% and 22.69%, respectively (P < 0.001). The GMTs of nAbs and IgG antibodies for nine HPV types in both 270ug and 360ug groups showed an obvious rise at month 7. For HPV31/33/45/52/58, the GMTs of nAbs in both 270μg and 360μg groups were higher than those in positive control group, with the 95% CIs lower bounds of GMT ratios all greater than 1. Compared to positive control group, HPV 6 and 18 achieved non-inferiority criteria for GMT in both dose groups. However, the GMT ratio of HPV 16 in the 270μg group was 0.46 (0.38-0.55), and HPV 16 and 11 in the 360μg group were 0.48 (0.40-0.58) and 0.53 (0.46-0.60) respectively. The SCRs of nAbs for HPV6/11/16/18 in the three groups were 100%, with the 95% CIs lower bound for SCR differences ranged from -2.55% to -1.64%. Conclusion: The candidate 9vHPV vaccine well tolerated and immunogenic, supporting further evaluation for efficacy and safety in larger populations. Clinical trial registration: ClinicalTrials.gov, identfier NCT05694728.