Shengli Xia1, Jialiang Du2, Jia Su1, Yueyue Liu2, Lili Huang1, Qingchuan Yu2, Zhiqiang Xie1, Jiamei Gao2, Bianli Xu1, Xuejun Gao3, Tai Guo2, Yan Liu4, Xu Zhou5, Huan Yang6. 1. Henan Center for Disease Control and Prevention, Zhengzhou 450000, China. 2. National Institutes for Food and Drug Control, Beijing 102629, China. 3. Lanzhou Institute of Biological Products Co Ltd, Lanzhou 730046, China. 4. National Institutes for Food and Drug Control, Beijing 102629, China. Electronic address: liuyan418@nifdc.org.cn. 5. Lanzhou Institute of Biological Products Co Ltd, Lanzhou 730046, China. Electronic address: kathzhou@sina.com. 6. Center for Drug Evaluation, National Medical Products Administration, Beijing 100022, China. Electronic address: 13691354049@163.com.
Abstract
BACKGROUND: A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy, immunogenicity and safety of a novel trivalent live human-lamb reassortant rotavirus vaccine (LLR3) against rotavirus gastroenteritis (RVGE). METHODS:Healthy children aged 6-13 weeks were enrolled and randomized (1:1) to either 3 oral doses of LLR3 or placebo according to a 0, 1, 2 month schedule. The objectives were to evaluate vaccine efficacy (VE) against RVGE of any-severity, severe RVGE (sRVGE) and inpatient caused by rotavirus serotypes contained in the vaccine and not contained in the vaccine after the third dose. Immunogenicity was also assayed in a subgroup. All adverse events (AEs) were collected from 30 min after each dose for immediate reaction, even to the entire study period, including the serious AEs (SAEs) and intussusception. RESULTS:VE against RVGE of any-severity, sRVGE and inpatient caused by any serotype was 56.6% (95% CI: 50.7, 61.8), 70.3% (95% CI: 60.6, 77.6) and 74.0% (95% CI: 57.5, 84.1) respectively. VE against RVGE of any-severity, sRVGE caused by serotypes not contained in vaccine were 54.2% (95% CI: 47.5, 60.1) and 70.4% (95% CI: 60.4, 77.9). The rate of seroconversion and four-fold increase of rotavirus serotype G2-, G3-, andG4-specific IgA is 60.8%, 58.0%, and 60.6% in vaccine group, which was higher than 21.35%, 22.7%, and 23.1% in placebo group (p < 0.0001 for G2, G3, G4), as well as the Geometric Mean Titer (GMT). Through the entire trial, 65.91% and 67.79% of participants reported at least one AE, and 0.02% and 0.02% reported SAEs in the vaccine and placebo groups, respectively. Two intussusception cases were reported both in vaccine and placebo group. CONCLUSIONS: In Chinese infants, LLR3 provided a substantial protection against RVGE of any-severity, sRVGE and inpatient caused by any serotype, and showed well immunogenicity and safety.
RCT Entities:
BACKGROUND: A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy, immunogenicity and safety of a novel trivalent live human-lamb reassortant rotavirus vaccine (LLR3) against rotavirus gastroenteritis (RVGE). METHODS: Healthy children aged 6-13 weeks were enrolled and randomized (1:1) to either 3 oral doses of LLR3 or placebo according to a 0, 1, 2 month schedule. The objectives were to evaluate vaccine efficacy (VE) against RVGE of any-severity, severe RVGE (sRVGE) and inpatient caused by rotavirus serotypes contained in the vaccine and not contained in the vaccine after the third dose. Immunogenicity was also assayed in a subgroup. All adverse events (AEs) were collected from 30 min after each dose for immediate reaction, even to the entire study period, including the serious AEs (SAEs) and intussusception. RESULTS: VE against RVGE of any-severity, sRVGE and inpatient caused by any serotype was 56.6% (95% CI: 50.7, 61.8), 70.3% (95% CI: 60.6, 77.6) and 74.0% (95% CI: 57.5, 84.1) respectively. VE against RVGE of any-severity, sRVGE caused by serotypes not contained in vaccine were 54.2% (95% CI: 47.5, 60.1) and 70.4% (95% CI: 60.4, 77.9). The rate of seroconversion and four-fold increase of rotavirus serotype G2-, G3-, and G4-specific IgA is 60.8%, 58.0%, and 60.6% in vaccine group, which was higher than 21.35%, 22.7%, and 23.1% in placebo group (p < 0.0001 for G2, G3, G4), as well as the Geometric Mean Titer (GMT). Through the entire trial, 65.91% and 67.79% of participants reported at least one AE, and 0.02% and 0.02% reported SAEs in the vaccine and placebo groups, respectively. Two intussusception cases were reported both in vaccine and placebo group. CONCLUSIONS: In Chinese infants, LLR3 provided a substantial protection against RVGE of any-severity, sRVGE and inpatient caused by any serotype, and showed well immunogenicity and safety.