ABSTRACT
The oral hexavalent live human-bovine reassortant rotavirus vaccine (RV6) developed by Wuhan Institute of Biological Products Co., Ltd (WIBP) has finished a randomized, placebo-controlled phase III clinical trial in four provinces of China in 2021. The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants. During the phase III clinical trial (2019-2021), 200 rotavirus-positive fecal samples from children with RV gastroenteritis (RVGE) were further studied. Using reverse transcription-polymerase chain reaction and high-throughput sequencing, VP7 and VP4 sequences were obtained and their genetic characteristics, as well as the differences in antigenic epitopes of VP7, were analyzed in detail. Seven rotavirus genotypes were identified. The predominant rotavirus genotype was G9P [8] (77.0%), followed by prevalent strains G8P [8] (8.0%), G3P [8] (3.5%), G3P [9] (1.5%), G1P [8] (1.0%), G2P [4] (1.0%), and G4P [6] (1.0%). The amino acid sequence identities of G1, G2, G3, G4, G8, and G9 genotypes of isolates compared to the vaccine strains were 98.8%, 98.2%-99.7%, 88.4%-99.4%, 98.2%, 94.2%-100%, and 93.9%-100%, respectively. Notably, the vaccine strains exhibited high similarity in amino acid sequence, with only minor differences in antigenic epitopes compared to the Chinese endemic strains. This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Animals , Cattle , Child , Humans , Infant , Antigens, Viral/genetics , Capsid Proteins/genetics , China , Epitopes/genetics , Feces , Genotype , Phylogeny , RNA, Viral/genetics , Rotavirus/genetics , Vaccines, Combined , Randomized Controlled Trials as Topic , Clinical Trials, Phase III as TopicABSTRACT
A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine (HRV) against rotavirus gastroenteritis (RVGE). A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV (n â= â3200) or placebo (n â= â3200) group. All the subjects received three oral doses of vaccine four weeks apart. The vaccine efficacy (VE) against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season. VE against severe RVGE, VE against RVGE hospitalization caused by serotypes contained in HRV, and VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated. All adverse events (AEs) were collected for 30 days after each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21% (95%CI: 53.31-79.69). VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36% (95%CI: 78.45-96.53) and 89.21% (95%CI: 64.51-96.72) respectively. VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88% (95%CI: 49.11-72.92), 85.51% (95%CI: 72.74-92.30) and 83.68% (95%CI: 61.34-93.11). Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable. There was no significant difference in incidences of SAEs in HRV and placebo groups. This study shows that this hexavalent reassortant rotavirus vaccine is an effective, well-tolerated, and safe vaccine for Chinese infants.
