Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial
Summary: Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537022003261 |
| _version_ | 1818163388204711936 |
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| author | Yeqing Tong Xinyue Zhang Jinhua Chen Wei Chen Zhao Wang Qiong Li Kai Duan Sheng Wei Beifang Yang Xiaoai Qian Jiahong Li Lianju Hang Shaoyong Deng Xinguo Li Changfu Guo Heng Shen Yan Liu Peng Deng Tingbo Xie Qingliang Li Li Li Hongqiao Du Qunying Mao Fan Gao Weiwei Lu Xuhua Guan Jiao Huang Xiuling Li Xiaoqi Chen |
| author_facet | Yeqing Tong Xinyue Zhang Jinhua Chen Wei Chen Zhao Wang Qiong Li Kai Duan Sheng Wei Beifang Yang Xiaoai Qian Jiahong Li Lianju Hang Shaoyong Deng Xinguo Li Changfu Guo Heng Shen Yan Liu Peng Deng Tingbo Xie Qingliang Li Li Li Hongqiao Du Qunying Mao Fan Gao Weiwei Lu Xuhua Guan Jiao Huang Xiuling Li Xiaoqi Chen |
| author_sort | Yeqing Tong |
| collection | DOAJ |
| description | Summary: Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration. Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345). Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%–100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%–99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%–100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%–2.86%) and -0.34% (95%CI: -2.78%–2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00–3.00) and 1.00 (95%CI: 0.75–1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines. Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated. Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd. |
| first_indexed | 2024-12-11T16:48:46Z |
| format | Article |
| id | doaj.art-6b17de130eaf417ea374c61baaf763d4 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-12-11T16:48:46Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-6b17de130eaf417ea374c61baaf763d42022-12-22T00:58:09ZengElsevierEClinicalMedicine2589-53702022-10-0152101596Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trialYeqing Tong0Xinyue Zhang1Jinhua Chen2Wei Chen3Zhao Wang4Qiong Li5Kai Duan6Sheng Wei7Beifang Yang8Xiaoai Qian9Jiahong Li10Lianju Hang11Shaoyong Deng12Xinguo Li13Changfu Guo14Heng Shen15Yan Liu16Peng Deng17Tingbo Xie18Qingliang Li19Li Li20Hongqiao Du21Qunying Mao22Fan Gao23Weiwei Lu24Xuhua Guan25Jiao Huang26Xiuling Li27Xiaoqi Chen28Hubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaXiangzhou District Centre for Disease Control and Prevention, Wuhan, ChinaXiangzhou District Centre for Disease Control and Prevention, Wuhan, ChinaXiangzhou District Centre for Disease Control and Prevention, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaWuhan Institute of Biological Products Co., Ltd, Wuhan, ChinaNational Institutes for Food and Drug Control, Beijing, ChinaNational Institutes for Food and Drug Control, Beijing, ChinaNational Vaccine &Serum Institute, Beijing, ChinaHubei Provincial Centre for Disease Control and Prevention, Wuhan, China; Corresponding authors.Centre for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China; Corresponding authors.Shanghai Institute of Biological Products Co., Ltd, Shanghai, China; Corresponding authors.Wuhan Institute of Biological Products Co., Ltd, Wuhan, China; Corresponding authors.Summary: Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration. Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345). Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%–100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%–99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%–100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%–2.86%) and -0.34% (95%CI: -2.78%–2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00–3.00) and 1.00 (95%CI: 0.75–1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines. Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated. Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.http://www.sciencedirect.com/science/article/pii/S2589537022003261Enterovirus 71 vaccineHand, foot and mouth diseaseImmunogenicitySafety |
| spellingShingle | Yeqing Tong Xinyue Zhang Jinhua Chen Wei Chen Zhao Wang Qiong Li Kai Duan Sheng Wei Beifang Yang Xiaoai Qian Jiahong Li Lianju Hang Shaoyong Deng Xinguo Li Changfu Guo Heng Shen Yan Liu Peng Deng Tingbo Xie Qingliang Li Li Li Hongqiao Du Qunying Mao Fan Gao Weiwei Lu Xuhua Guan Jiao Huang Xiuling Li Xiaoqi Chen Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial EClinicalMedicine Enterovirus 71 vaccine Hand, foot and mouth disease Immunogenicity Safety |
| title | Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial |
| title_full | Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial |
| title_fullStr | Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial |
| title_full_unstemmed | Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial |
| title_short | Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial |
| title_sort | immunogenicity and safety of an enterovirus 71 vaccine in children aged 36 71 months a double blind randomised similar vaccine controlled non inferiority phase iii trial |
| topic | Enterovirus 71 vaccine Hand, foot and mouth disease Immunogenicity Safety |
| url | http://www.sciencedirect.com/science/article/pii/S2589537022003261 |
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