Giuseppe
Emeritus
[Source: The Lancet, full text: (LINK). Abstract, edited.]
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The Lancet, Early Online Publication, 29 May 2013
doi:10.1016/S0140-6736(13)61049-1
Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
Original Text
Feng-Cai Zhu MSc a b, Fan-Yue Meng MSc a, Jing-Xin Li MSc a b, Xiu-Ling Li MSc c, Qun-Ying Mao PhD d, Hong Tao BS a, Yun-Tao Zhang PhD c, Xin Yao PhD d, Kai Chu MSc a, Qing-Hua Chen MSc c, Yue-Mei Hu BS a, Xing Wu MSc d, Pei Liu PhD e, Lin-Yang Zhu BS f, Fan Gao MSc d, Hui Jin PhD e, Yi-Juan Chen MSc e, Yu-Ying Dong MSc e, Yong-Chun Liang BS g, Nian-Min Shi MSc h, Heng-Ming Ge BS i, Lin Liu BS j, Sheng-Gen Chen BS g, Xing Ai MSc h, Zhen-Yu Zhang BS i, Yu-Guo Ji BS g, Feng-Ji Luo MSc h, Xiao-Qin Chen BS i, Ya Zhang BS j, Li-Wen Zhu BS g, Zheng-Lun Liang PhD d, Xin-Liang Shen MSc c
Summary
Background
A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine.
Methods
We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6?35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247.
Findings
10 245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90?0% (95% CI 67?1?96?9) against EV71-associated HFMD (p=0?0001) and 80?4% (95% CI 58?2?90?8) against EV71-associated disease (p<0?0001). Serious adverse events were reported by 62 of 5117 (1?2%) participants in the vaccine group versus 75 of 5123 (1?5%) in the placebo group (p=0?27). Adverse events occurred in 3644 (71?2%) versus 3603 (70?3%; p=0?33).
Interpretation
EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity.
Funding
China's 12?5 National Major Infectious Disease Program, Beijing Vigoo Biological.
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a Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China; b Department of Clinical Microbiology and Immunology, College of Pharmacy, Third Military Medical University & National Engineering Research Center for Immunological Products, Chongqing, China; c Beijing Vigoo Biological, Beijing, China; d National Institute for Food and Drug Control, Beijing, China; e School of Public Health, Southeast University, Nanjing, Jiangsu, China; f Lianyungang City Center for Disease Control and Prevention, Lianyungang, Jiangsu, China; g Baoying County Center for Disease Control and Prevention, Yangzhou, Jiangsu, China; h Chaoyang District Center for Disease Control and Prevention, Beijing, China; i Donghai County Center for Disease Control and Prevention, Lianyungang, Jiangsu, China; j Pizhou County Center for Disease Control and Prevention, Xuzhou, Jiangsu, China
Correspondence to: Feng-Cai Zhu, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Road, Nanjing 210009, Jiangsu, China; Zheng-Lun Liang, National Institute for Food and Drug Control, Tiantanxili, Beijing 100050, China; Xin-Liang Shen, Beijing Vigoo Biological, Sanjianfangnanli, ChaoYang District, Beijing 100024, China
-doi:10.1016/S0140-6736(13)61049-1
Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
Original Text
Feng-Cai Zhu MSc a b, Fan-Yue Meng MSc a, Jing-Xin Li MSc a b, Xiu-Ling Li MSc c, Qun-Ying Mao PhD d, Hong Tao BS a, Yun-Tao Zhang PhD c, Xin Yao PhD d, Kai Chu MSc a, Qing-Hua Chen MSc c, Yue-Mei Hu BS a, Xing Wu MSc d, Pei Liu PhD e, Lin-Yang Zhu BS f, Fan Gao MSc d, Hui Jin PhD e, Yi-Juan Chen MSc e, Yu-Ying Dong MSc e, Yong-Chun Liang BS g, Nian-Min Shi MSc h, Heng-Ming Ge BS i, Lin Liu BS j, Sheng-Gen Chen BS g, Xing Ai MSc h, Zhen-Yu Zhang BS i, Yu-Guo Ji BS g, Feng-Ji Luo MSc h, Xiao-Qin Chen BS i, Ya Zhang BS j, Li-Wen Zhu BS g, Zheng-Lun Liang PhD d, Xin-Liang Shen MSc c
Summary
Background
A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine.
Methods
We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6?35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247.
Findings
10 245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90?0% (95% CI 67?1?96?9) against EV71-associated HFMD (p=0?0001) and 80?4% (95% CI 58?2?90?8) against EV71-associated disease (p<0?0001). Serious adverse events were reported by 62 of 5117 (1?2%) participants in the vaccine group versus 75 of 5123 (1?5%) in the placebo group (p=0?27). Adverse events occurred in 3644 (71?2%) versus 3603 (70?3%; p=0?33).
Interpretation
EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity.
Funding
China's 12?5 National Major Infectious Disease Program, Beijing Vigoo Biological.
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a Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China; b Department of Clinical Microbiology and Immunology, College of Pharmacy, Third Military Medical University & National Engineering Research Center for Immunological Products, Chongqing, China; c Beijing Vigoo Biological, Beijing, China; d National Institute for Food and Drug Control, Beijing, China; e School of Public Health, Southeast University, Nanjing, Jiangsu, China; f Lianyungang City Center for Disease Control and Prevention, Lianyungang, Jiangsu, China; g Baoying County Center for Disease Control and Prevention, Yangzhou, Jiangsu, China; h Chaoyang District Center for Disease Control and Prevention, Beijing, China; i Donghai County Center for Disease Control and Prevention, Lianyungang, Jiangsu, China; j Pizhou County Center for Disease Control and Prevention, Xuzhou, Jiangsu, China
Correspondence to: Feng-Cai Zhu, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Road, Nanjing 210009, Jiangsu, China; Zheng-Lun Liang, National Institute for Food and Drug Control, Tiantanxili, Beijing 100050, China; Xin-Liang Shen, Beijing Vigoo Biological, Sanjianfangnanli, ChaoYang District, Beijing 100024, China
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