Saluja Tarun, Palkar Sonali, Misra Puneet, Gupta Madhu, Venugopal Potula, Sood Ashwani Kumar, Dhati Ravi Mandyam, Shetty Avinash, Dhaded Sangappa Malappa, Agarkhedkar Sharad, Choudhury Amlan, Kumar Ramesh, Balasubramanian Sundaram, Babji Sudhir, Adhikary Lopa, Dupuy Martin, Chadha Sangeet Mohan, Desai Forum, Kukian Darshna, Patnaik Badri Narayan, Dhingra Mandeep Singh
Shantha Biotechnics Pvt. Ltd., Hyderabad, India.
Bharati Vidyapeeth Deemed University Medical College, Pune, India.
Vaccine. 2017 Jun 16;35(28):3575-3581. doi: 10.1016/j.vaccine.2017.05.019. Epub 2017 May 20.
Rotavirus remains the leading cause of diarrhoea among children <5years. We assessed immunogenic non-inferiority of a tetravalent bovine-human reassortant rotavirus vaccine (BRV-TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5.
Phase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6-8, 10-12, and 14-16weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval [CI]) was above -10%. Each subject was evaluated for solicited adverse events 7days and unsolicited & serious adverse events 28days following each dose of vaccination.
Of 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, -14.08% (95%CI: -20.4; -7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the -10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles.
BRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when administered concomitantly with routine pediatric antigens in infants.
轮状病毒仍是5岁以下儿童腹泻的主要病因。我们评估了一种四价牛 - 人重配轮状病毒疫苗（BRV-TV）相对于已获许可的人 - 牛五价轮状病毒疫苗RV5的免疫原性非劣效性。
一项III期单盲研究（家长 blinded），将健康婴儿随机分组（1:1），在6 - 8周、10 - 12周和14 - 16周龄时接受三剂BRV-TV或RV5。所有婴儿同时接种已获许可的白喉、破伤风、百日咳、乙型肝炎、b型流感嗜血杆菌结合疫苗（DTwP-HepB-Hib）和口服脊髓灰质炎疫苗（OPV）。根据抗轮状病毒血清IgA血清反应的组间差异（主要终点）以及对DTwP-HepB-Hib和OPV疫苗的血清保护/血清反应率评估免疫原性非劣效性。血清反应定义为从基线到第3剂后第28天滴度增加≥4倍。如果组间差异（基于95%置信区间[CI]的下限）高于 - 10%，则判定为非劣效。在每次接种疫苗后7天评估主动不良事件，28天评估被动和严重不良事件。
在1195名筛查的婴儿中，1182名被随机分组（590名接受BRV-TV；592名接受RV5）。未确立轮状病毒血清IgA血清反应的非劣效性：BRV-TV组为47.1%（95%CI：42.8；51.5），RV5组为61.2%（95%CI：56.8；65.5）；组间差异为 - 14.08%（95%CI： - 20.4； - 7.98）。第3剂后第28天，BRV-TV组和RV5组的血清IgA几何平均浓度分别为28.4和50.1U/ml。对于所有DTwP-HepB-Hib和OPV抗原，两组均引发了血清保护/血清反应，且组间 - 10%的非劣效性标准得到满足。有16例严重不良事件，BRV-TV组10例，RV5组6例；均未分类为与疫苗相关。两组的疫苗安全性概况相似。
在婴儿中与常规儿科抗原同时接种时，BRV-TV具有免疫原性，但未达到相对于RV5的免疫原性非劣效性标准。
