Effect evaluation of co-administration with bivalent human papilloma virus vaccine and hepatitis E virus vaccine
CHEN Maofang1, WU Ailan1, XU Yuechen1, JIN Xujing1, ZHOU Pinpu1, ZHANG Jing1, CHEN Xiaoqing1, JIN Feihua2, WU Jianfeng1
1. Dongyang Center for Disease Control and Prevetion (Dongyang Institute of Public Health Supervision), Dongyang, Zhejiang 322100, China; 2. Hengdian Wenrong Hospital, Dongyang, Zhejiang 322100, China
Abstract：Objective To evaluate the immunogenicity and safety of co-administration with bivalent human papillomavirus (HPV) vaccine and hepatitis E virus (HEV) vaccine, so as to provide reference for optimizing the vaccination schedule. Methods Females aged 18 to 25 years were recruited from September to October 2021 in Hengdian College of Film & Television in Zhejiang Province and randomly divided into the HPV+HEV group, the HPV group, and the HEV group. The vaccination procedures were one dose each at 0, 1, and 6 months. Immunogenicity was evaluated by detecting the geometric mean titers (GMT) of HPV16 IgG, HPV18 IgG, and/or HEV IgG antibodies before the first vaccination and one month after the full course of immunization, and comparing the difference in seroconversion, and the GMT ratio. The non-inferiority margin was set at a seroconversion difference of ≤5%, and the lower limit of the 95%CI of the GMT ratio was >0.5. Safety was evaluated by collecting conjunctive local reactions/events and systemic reactions/events within 7 days after each dose, non-conjunctive adverse events within 30 days after each dose, and serious adverse events throughout the observation period (0 to 7 months). Results A total of 240 females were included, among whom 236 completed the full vaccination program, including 79 in the HPV+HEV group, 77 in the HPV group, and 80 in the HEV group. One month after the full course of immunization, the seroconversion rates of HPV16 IgG and HPV18 IgG antibodies in both the HPV+HEV group and the HPV group were 100%, and the differences in seroconversion rates were 0 (95%CI: -3.39%-+∞). The seroconversion rates of HEV IgG antibodies in both the HPV+HEV group and the HEV group were 100%, and the difference in seroconversion rates was 0 (95%CI: -3.27%-+∞). The GMT of HPV16 IgG and HPV18 IgG antibodies in the HPV+HEV group was 393.88 and 284.86 IU/mL respectively, which was not inferior to 489.39 and 341.24 IU/mL in the HPV group, and the GMT ratios were 0.80 (95%CI: 0.66-+∞) and 0.83 (95%CI: 0.68-+∞), respectively. The GMT of HEV IgG in the HPV+HEV group was 13.55 U/mL, which was not inferior to 12.72 U/mL in the HEV group, and the GMT ratio was 1.07 (95%CI: 0.92-+∞). The incidences of pain, pruritus, and induration in the HPV+HEV group were 54.43%, 21.52% and 40.51% respectively, which were significantly higher than 10.39%, 0, and 0 in the HPV group (all P<0.05). The incidences of redness/swelling, muscle pain/general weakness in the HPV+HEV group were 2.53% and 0, respectively, which were significantly lower than 12.50% and 16.25% in the HEV group (both P<0.05). Conclusion The co-administration of the bivalent HPV vaccine and HEV vaccine is not inferior to individual vaccination in terms of immunogenicity and safety, and the vaccination plan can be optimized through co-administration.
[1] 陈晓静,李雷.甲基化检测用于子宫颈癌筛查及预后管理的研究进展[J].中华妇产科杂志,2024,59(8):646-650. CHEN X J,LI L.Research progress of methylation detection in cervical cancer screening and prognosis management[J].Chin J Obstet Gynecol,2024,59(8):646-650.(in Chinese) [2] LI J,SHI L W,LI K,et al.Comparison of the safety and persistence of immunogenicity of bivalent HPV16/18 vaccine in healthy 9-14-year-old and 18-26-year-old Chinese females:a randomized,double-blind,non-inferiority clinical trial[J].Vaccine,2023,41(48):7212-7219. [3] HUANG S J,ZHANG X F,SU Y Y,et al.Long-term efficacy of a recombinant hepatitis E vaccine in adults:10-year results from a randomised,double-blind,placebo-controlled,phase 3 trial[J].Lancet,2024,403(10429):813-823. [4] PERON J M,LARRUE H,IZOPET J,et al.The pressing need for a global HEV vaccine[J].J Hepatol,2023,79(3):876-880. [5] BONANNI P,STEFFEN R,SCHELLING J,et al.Vaccine co-administration in adults:an effective way to improve vaccination coverage[J].Hum Vaccin Immunother,2023,19(1):1-6. [6] SUN D P,YU D,DU Z H,et al.Immunogenicity and safety of a live attenuated varicella vaccine co-administered with inactive hepatitis A vaccine:a phase 4,single-center,randomized,controlled trial[J].Hum Vaccin Immunother,2023,19(1):1-8. [7] GILCA V,SAUVAGEAU C,BOULIANNE N,et al.Immunogenicity of quadrivalent HPV and combined hepatitis A and B vaccine when co-administered or administered one month apart to 9-10 year-old girls according to 0-6 month schedule[J].Hum Vaccin Immunother,2014,10(8):2438-2445. [8] 唐欣然,黄耀华,王杨,等.Newcombe-Wilson得分方法在有效率为100%非劣效临床试验中的应用[J].中华疾病控制杂志,2015,19(2):190-192. TANG X R,HUANG Y H,WANG Y,et al.Application of Newcombe-Wilson score method in non-inferiority clinical trials with full rates of success[J].Chin J Dis Control Prev,2015,19(2):190-192.(in Chinese) [9] QIAO Y L,WU T,LI R C,et al.Efficacy,safety,and immunogenicity of an escherichia coli-produced bivalent human papillomavirus vaccine:an interim analysis of a randomized clinical trial[J].J Natl Cancer Inst,2020,112(2):145-153. [10] BÖRNER N,MÜHLBERGER N,JELINEK T.Tolerability of multiple vaccinations in travel medicine[J].J Travel Med,2003,10(2):112-116. [11] TURNER N,GRANT C,GOODYEAR-SMITH F,et al.Seize the moments:missed opportunities to immunize at the family practice level[J].Fam Pract,2009,26(4):275-278. [12] 窦倩如,黄翠敏,曹霞,等.海南省女性HPV疫苗相关知识和接种意愿调查[J].预防医学,2023,35(4):359-364. DOU Q R,HUANG C M,CAO X,et al.Awareness of human papillomavirus vaccine knowledge and willingness to receive human papillomavirus vaccination among women in Hainan Province[J].China Prev Med J,2023,35(4):359-364.(in Chinese)
