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, 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

Abstract

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.

Keywords: foot and mouth disease; hand; inactivated enterovirus 71 vaccine; separate administration; simultaneous administration.

Conflict of interest statement

Xiaoming Yang, Haiping Chen, Yanhui Xiao, Min Zhang and Xuanwen Shi are employees of the China National Biotec Group Company Limited. Xiaoqi Chen and Wei Chen are employees of the Wuhan Institute of Biological Products Co, Ltd., which developed and provided the EV71 vaccine. No other disclosures were reported.

Figures

Figure 1
Figure 1
Flowchart of blood drawing and vaccinations in five study groups. Group A: EV71 vaccine and hepatitis B virus vaccine simultaneous administration group; Group B: EV71 vaccine and group A meningococcal polysaccharide vaccine simultaneous administration group; Group C: EV71 vaccine and measles-rubella combined vaccine simultaneous administration group; Group D: EV71 vaccine and Japanese encephalitis vaccine simultaneous administration group; Group E: EV71 vaccine separate administration group. EV71 = Inactivated enterovirus 71 vaccine; HepB = Hepatitis B virus vaccine; MPSV-A = Group A meningococcal polysaccharide vaccine; MR = measles-rubella combined vaccine; JE-L = Live, attenuated Japanese encephalitis vaccine.
Figure 2
Figure 2
Trial profile, per-protocol analyses (PPS), China, 2018 to 2019.
Figure 3
Figure 3
Differences in the proportion of seroconversion for simultaneous administration groups versus separate administration groups, China 2018 to 2019. Differences in the proportion of seroconversion were measured between simultaneous groups (Group A, Group B, Group C, and Group D) and separate group (Group E) with two-sided 95% CIs.

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Source: PubMed

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