a Enteric Virus Group, Murdoch Children's Research Institute , Parkville , VIC , Australia.
b Rotavirus Program, Murdoch Children's Research Institute , Parkville , VIC , Australia.
Hum Vaccin Immunother. 2018;14(8):2082-2087. doi: 10.1080/21645515.2018.1467202. Epub 2018 May 31.
Serum rotavirus IgA responses are an imperfect non-mechanistic correlate of protection, and the lack of an accurate serological marker is a challenge to the development of new rotavirus vaccines. Serological responses to rotavirus NSP2 occur following wild-type infection; however, it is unknown if serological responses to NSP2 occur following administration of rotavirus vaccines. The phase IIa immunogenicity trial of RV3-BB provided an opportunity to investigate the serological responses to NSP2 following vaccination. Healthy, full-term babies (n = 96) were previously recruited as part of a phase IIa safety and immunogenicity trial in Dunedin, New Zealand between January 2012 and April 2014. Participants received three doses of oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Serum IgA and IgG antibody responses to total RV3-BB and NSP2 protein (RV3-BB) were assessed using ELISA. Despite significant serum IgA response against total RV3-BB, we were unable to demonstrate a significant serological response to NSP2 in participants receiving RV3-BB when compared to placebo. Heterotypic antibodies against multiple NSP2 genotypes were detected following RV3-BB vaccination. Our data demonstrates that while serological responses to NSP2 were detectable in a subset of participants, it is a less useful marker when compared to total rotavirus serum IgA response.
血清轮状病毒 IgA 反应是一种不完善的非机制相关性保护，缺乏准确的血清学标志物是开发新的轮状病毒疫苗的挑战。野生型感染后会发生针对轮状病毒 NSP2 的血清学反应；然而，尚不清楚接种轮状病毒疫苗后是否会发生针对 NSP2 的血清学反应。RV3-BB 的 IIa 期免疫原性试验为研究接种疫苗后 NSP2 的血清学反应提供了机会。此前，在 2012 年 1 月至 2014 年 4 月期间，在新西兰达尼丁进行了一项 IIa 期安全性和免疫原性试验，招募了健康足月婴儿（n=96）作为该试验的一部分。参与者接受了三剂口服 RV3-BB 疫苗，第一剂在出生后 0-5 天（新生儿方案）或出生后约 8 周（婴儿方案）给予，或给予安慰剂（安慰剂方案）。使用 ELISA 评估针对总 RV3-BB 和 NSP2 蛋白（RV3-BB）的血清 IgA 和 IgG 抗体反应。尽管针对总 RV3-BB 有明显的血清 IgA 反应，但与安慰剂相比，我们未能证明接受 RV3-BB 的参与者对 NSP2 有明显的血清学反应。接种 RV3-BB 后检测到针对多种 NSP2 基因型的异型抗体。我们的数据表明，虽然 NSP2 的血清学反应在一部分参与者中可检测到，但与总轮状病毒血清 IgA 反应相比，它是一种不太有用的标志物。
