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. 2019 Jun 21;63(4):582–591. doi: 10.1007/s11427-019-9547-7

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women

Yue-Mei Hu 1,#, Meng Guo 2,#, Chang-Gui Li 3,#, Kai Chu 1, Wen-Gang He 2, Jing Zhang 4, Jian-Xiang Gu 4, Juan Li 3, Hui Zhao 3, Xiang-Hong Wu 4, BiZhen Lin 5, Zhi-Jie Lin 5, Xing-Mei Yao 2, Ya-Fei Li 2, FeiXue Wei 2, Yue Huang 2, Ying-Ying Su 2, Feng-Cai Zhu 1, Shou-Jie Huang 2, Hui-Rong Pan 5, Ting Wu 2, Jun Zhang 2,✉, Ning-Shao Xia 2,✉
PMCID: PMC7223315  PMID: 31231780

Abstract

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9–14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15–17 years (n=149) and women aged 18–26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9–14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s11427-019-9547-7 and is accessible for authorized users.

Keywords: immunobridging, noninferiority, human papillomavirus, vaccine, Escherichia coli, girls

Electronic supplementary material

11427_2019_9547_MOESM1_ESM.docx (269.1KB, docx)

Supplementary material, approximately 272 KB.

11427_2019_9547_MOESM2_ESM.docx (24.2KB, docx)

Supplementary Table 1. Noninferiority Analysis of Seroconversion Rate in the ITT cohort

11427_2019_9547_MOESM3_ESM.docx (22.2KB, docx)

Supplementary Table 2. Noninferiority Analysis of Geometric Mean Concentrations (GMCs) in the PPS cohort

11427_2019_9547_MOESM4_ESM.docx (24.6KB, docx)

Supplementary Table 3. Noninferiority Analysis of Geometric Mean Concentrations (GMCs) in the ITT cohort

11427_2019_9547_MOESM5_ESM.docx (21KB, docx)

Supplementary Table 4. Noninferiority Analysis of Geometric Mean Concentrations (GMCs) in girls who received 2 doses vs 3 doses

11427_2019_9547_MOESM6_ESM.docx (25.4KB, docx)

Supplementary Table 5. Adverse Events Reported within 30 days after Each Dose

11427_2019_9547_MOESM7_ESM.docx (17.9KB, docx)

Supplementary Table 6. Listing of Serious Adverse Events (SAEs) reported during the study (From day 0 to month 7)

11427_2019_9547_MOESM8_ESM.docx (21.8KB, docx)

Supplementary Table 7. The Study inclusion and exclusion criteria for the study

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81673240, and U1705283), the Chinese National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX09308010, 2012ZX09101316), the Fujian Provincial Major Scientific and Technological Project (2015YZ0002) and Xiamen Innovax.

Footnotes

Compliance and ethics

M.G., B.-Z.L., Z.-J.L., and H.-R.P. report being either current or former employees of Xiamen Innovax. No other potential conflict of interest relevant to this article by the other authors was reported. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Contributed equally to this work

Contributor Information

Jun Zhang, Email: zhangj@xmu.edu.cn.

Ning-Shao Xia, Email: nsxia@xmu.edu.cn.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

11427_2019_9547_MOESM1_ESM.docx (269.1KB, docx)

Supplementary material, approximately 272 KB.

11427_2019_9547_MOESM2_ESM.docx (24.2KB, docx)

Supplementary Table 1. Noninferiority Analysis of Seroconversion Rate in the ITT cohort

11427_2019_9547_MOESM3_ESM.docx (22.2KB, docx)

Supplementary Table 2. Noninferiority Analysis of Geometric Mean Concentrations (GMCs) in the PPS cohort

11427_2019_9547_MOESM4_ESM.docx (24.6KB, docx)

Supplementary Table 3. Noninferiority Analysis of Geometric Mean Concentrations (GMCs) in the ITT cohort

11427_2019_9547_MOESM5_ESM.docx (21KB, docx)

Supplementary Table 4. Noninferiority Analysis of Geometric Mean Concentrations (GMCs) in girls who received 2 doses vs 3 doses

11427_2019_9547_MOESM6_ESM.docx (25.4KB, docx)

Supplementary Table 5. Adverse Events Reported within 30 days after Each Dose

11427_2019_9547_MOESM7_ESM.docx (17.9KB, docx)

Supplementary Table 6. Listing of Serious Adverse Events (SAEs) reported during the study (From day 0 to month 7)

11427_2019_9547_MOESM8_ESM.docx (21.8KB, docx)

Supplementary Table 7. The Study inclusion and exclusion criteria for the study

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