减毒活人类轮状病毒疫苗RIX4414可在婴儿中为抵抗具有或不具有共同G和P基因型的轮状病毒株提供临床保护：随机对照试验的综合分析

Live attenuated human rotavirus vaccine, RIX4414, provides clinical protection in infants against rotavirus strains with and without shared G and P genotypes: integrated analysis of randomized controlled trials.

作者信息

De Vos Beatrice, Han Htay Htay, Bouckenooghe Alain, Debrus Serge, Gillard Paul, Ward Richard, Cheuvart Brigitte

机构信息

GlaxoSmithKline Biologicals, Rixensart, Belgium.

出版信息

Pediatr Infect Dis J. 2009 Apr;28(4):261-6. doi: 10.1097/INF.0b013e3181907177.

DOI:10.1097/INF.0b013e3181907177

PMID:19289978

Abstract

BACKGROUND

: The 2-dose, oral live attenuated human G1P[8] rotavirus vaccine (RIX4414) is highly effective against rotavirus gastroenteritis caused by circulating G1 and non-G1 types. An integrated analysis on vaccine efficacy was undertaken to obtain more precise estimates of the overall protective effect of the RIX4414 vaccine against rotavirus gastroenteritis due to common rotavirus types (G1, G3, G4, G9, P[8]) and less commonly encountered strains such as G2P[4] across heterogenous settings.

METHODS

: The studies used in the integrated analysis were all previously reported randomized, double-blind, placebo-controlled, phase II and III trials with at least 1 report of rotavirus gastroenteritis in the efficacy follow-up period (up to 1 year of age or end of first RV epidemic season after vaccination). The integrated analysis was performed for all circulating rotavirus strains sharing G and/or P genotype and not sharing G or P genotype with the vaccine strain. Vaccine efficacy was estimated as 1 minus rate of rotavirus gastroenteritis relative to placebo, using exact Poisson rate ratio stratified by study.

RESULTS

: The integrated estimates for vaccine efficacy against severe rotavirus gastroenteritis were 87.43% (95% confidence interval [CI]: 78.89-92.86) for G1P[8] strains, 71.42% (95% CI: 20.12-91.11) for G2P[4] strains, 90.19% (95% CI: 55.51-98.94) for G3P[8] strains, 93.37% (95% CI: 51.50-99.85) for G4P[8] strains, and 83.76% (95% CI: 71.18-91.28) for G9P[8] strains. The integrated estimates for vaccine efficacies against rotavirus gastroenteritis of any severity were 82.57% (95% CI: 73.91-88.56) for G1P[8] strains, 81.04% (95% CI: 31.58-95.76) for G2P[4] strains, 87.66% (95% CI: 34.57-98.76) for G3P[8] strains, 84.86% (95% CI: 50.92-96.41) for G4P[8] strains, and 60.64% (95% CI: 38.15-74.96) for G9P[8] strains.

CONCLUSIONS

: Two doses of RIX4414 provide overall good clinical protection against all cases of rotavirus gastroenteritis and comparable, high clinical protection against severe rotavirus gastroenteritis caused by circulating rotavirus strains with and without G and P genotypes shared with the vaccine strain, such as G2P[4].

摘要

背景

两剂口服减毒活人类G1P[8]轮状病毒疫苗（RIX4414）对由流行的G1型和非G1型引起的轮状病毒肠胃炎具有高度有效性。开展了一项关于疫苗效力的综合分析，以更精确地估计RIX4414疫苗针对常见轮状病毒类型（G1、G3、G4、G9、P[8]）以及如G2P[4]等较少见毒株所致轮状病毒肠胃炎在不同环境下的总体保护效果。

方法

综合分析中所使用的研究均为先前报告的随机、双盲、安慰剂对照的II期和III期试验，在效力随访期（直至1岁或接种疫苗后首个轮状病毒流行季节结束）至少有1例轮状病毒肠胃炎报告。对所有与疫苗毒株共享G和/或P基因型以及不共享G或P基因型的流行轮状病毒株进行综合分析。疫苗效力估计为1减去相对于安慰剂的轮状病毒肠胃炎发生率，采用按研究分层的精确泊松率比。

结果

针对严重轮状病毒肠胃炎的疫苗效力综合估计值，G1P[8]毒株为87.43%（95%置信区间[CI]：78.89 - 92.86），G2P[4]毒株为71.42%（95%CI：20.12 - 91.11），G3P[8]毒株为90.19%（95%CI：55.51 - 98.94），G4P[8]毒株为93.37%（95%CI：51.50 - 99.85），G9P[8]毒株为83.76%（95%CI：71.18 - 91.28）。针对任何严重程度的轮状病毒肠胃炎的疫苗效力综合估计值，G1P[8]毒株为82.57%（95%CI：73.91 - 88.56），G2P[4]毒株为81.04%（95%CI：31.58 - 95.76），G3P[8]毒株为87.66%（95%CI：34.57 - 98.76），G4P[8]毒株为84.86%（95%CI：50.92 - 96.41），G9P[8]毒株为60.64%（95%CI：38.15 - 74.96）。