Immunogenicity and Safety of an Inactivated Enterovirus 71 Vaccine Administered Simultaneously with Hepatitis B Virus Vaccine, Group A Meningococcal Polysaccharide Vaccine, Measles-Rubella Combined Vaccine and Japanese Encephalitis Vaccine: A Multi-Center, Randomized, Controlled Clinical Trial in China
Xiaodong Liu,
Shaoying Chang,
Ruize Wang,
Yanhui Xiao,
Fangjun Li,
Qing Xu,
Shaobai Zhang,
Xiao Chen,
Shangxiao Zhang,
Min Zhang,
Xiaoqi Chen,
Qingfan Cao,
Xiaoyu Liu,
Hui Wang,
Daihong Zhan,
Haiping Chen,
Wei Chen,
Jianyong Jiang,
Chao Zhang,
Haijiao Wang,
Lidong Gao,
Xuanwen Shi,
Xiaoming Yang,
Aiqiang Xu
Affiliations
Xiaodong Liu
Shandong Provincial Center for Disease Control and Prevention, Jinan 250014, China
Shaoying Chang
Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, China
Ruize Wang
Shaanxi Provincial Center for Disease Control and Prevention, Xi’an 710054, China
Yanhui Xiao
China National Biotec Group Company Limited, Beijing 100024, China
Fangjun Li
Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
Qing Xu
Shandong Provincial Center for Disease Control and Prevention, Jinan 250014, China
Shaobai Zhang
Shaanxi Provincial Center for Disease Control and Prevention, Xi’an 710054, China
Xiao Chen
Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, China
Shangxiao Zhang
Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
Min Zhang
China National Biotec Group Company Limited, Beijing 100024, China
Xiaoqi Chen
Wuhan Institute of Biological Products Company Limited, Wuhan 430200, China
Qingfan Cao
Rushan City Center for Disease Control and Prevention, Rushan 264500, China
Xiaoyu Liu
Shaanxi Provincial Center for Disease Control and Prevention, Xi’an 710054, China
Hui Wang
Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, China
Daihong Zhan
Shimen County Center for Disease Control and Prevention, Changde 415300, China
Haiping Chen
China National Biotec Group Company Limited, Beijing 100024, China
Wei Chen
Wuhan Institute of Biological Products Company Limited, Wuhan 430200, China
Jianyong Jiang
Haiyang City Center for Disease Control and Prevention, Haiyang 265199, China
Chao Zhang
Shaanxi Provincial Center for Disease Control and Prevention, Xi’an 710054, China
Haijiao Wang
Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, China
Lidong Gao
Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
Xuanwen Shi
China National Biotec Group Company Limited, Beijing 100024, China
Xiaoming Yang
China National Biotec Group Company Limited, Beijing 100024, China
Aiqiang Xu
Shandong Provincial Center for Disease Control and Prevention, Jinan 250014, China
Background: The aim of this study was to investigate the immunogenicity and safety of the enterovirus 71 vaccine (EV71 vaccine) administered alone or simultaneously. Methods: A multi-center, open-label, randomized controlled trial was performed involving 1080 healthy infants aged 6 months or 8 months from Shandong, Shanxi, Shaanxi, and Hunan provinces. These infants were divided into four simultaneous administration groups and EV71 vaccine separate administration group. Blood samples were collected from the infants before the first vaccination and after the completion of the vaccination. This trial was registered in the Clinical Trials Registry (NCT03519568). Results: A total of 895 were included in the per-protocol analysis. The seroconversion rates of antibodies against EV71 in four simultaneous administration groups (98.44% (189/192), 94.57% (122/129), 99.47% (187/188) and 98.45% (190/193)) were non-inferior to EV71 vaccine separate administration group (97.93% [189/193]) respectively. Fever was the most common adverse event, the pairwise comparison tests showed no difference in the incidence rate of solicited, systemic or local adverse events. Three serious adverse events related to the vaccination were reported. Conclusions: The evidence of immunogenicity and safety supports that the EV71 vaccine administered simultaneously with vaccines need to be administered during the same period of time recommended in China.
