METHODS: 150 participants were randomly selected from the 447 children who participated in the RTS,S/AS01 phase IIb clinical trial in 2007 from Kilifi-Kenya. Cumulatively, the retrospective follow-up period was 93 months with annual plasma samples collection. The levels of anti-CSP IgM, total IgG, IgG1, IgG2, IgG3, and IgG4 antibodies were then determined using an enzyme-linked immunosorbent assay.
RESULTS: RTS,S/AS01 induced high levels of anti-CSP IgG antibodies which exhibited a rapid waning over 6.5 months post-vaccination, followed by a slower decay over the subsequent years. RTS,S/AS01-induced anti-CSP IgG antibodies remained elevated above the control group levels throughout the 7 years follow-up period. The anti-CSP IgG antibodies were mostly IgG1, IgG3, IgG2, and to a lesser extent IgG4. IgG2 predominated in later timepoints. RTS,S/AS01 also induced high levels of anti-CSP IgM antibodies which increased above the control group levels by month 3. The controls exhibited increasing levels of the anti-CSP IgM antibodies which caught up with the RTS,S/AS01 vaccinees levels by month 21. In contrast, there were no measurable anti-CSP IgG antibodies among the controls.
CONCLUSIONS: RTS,S/AS01-induced anti-CSP IgG antibodies kinetics are consistent with long-lived but waning vaccine efficacy. Natural exposure induces anti-CSP IgM antibodies in children, which increases with age, but does not induce substantial levels of anti-CSP IgG antibodies.
方法:从参加RTS的447名儿童中随机选择150名参与者,2007年在肯尼亚基利菲进行的S/AS01IIb期临床试验。累计,回顾性随访期为93个月,每年采集血浆样本.抗CSPIgM的水平,总IgG,然后使用酶联免疫吸附测定测定IgG1、IgG2、IgG3和IgG4抗体。
结果:RTS,S/AS01诱导高水平的抗CSPIgG抗体,在疫苗接种后6.5个月内表现出快速下降,在随后的几年中,衰减速度较慢。RTS,S/AS01诱导的抗CSPIgG抗体在整个7年随访期间保持高于对照组水平。抗CSPIgG抗体主要是IgG1、IgG3、IgG2,并且在较小程度上是IgG4。IgG2在稍后的时间点中占主导地位。RTS,S/AS01还诱导高水平的抗CSPIgM抗体,其在第3个月时增加到对照组水平以上。对照显示与RTS追赶的抗CSPIgM抗体水平增加,第21个月的S/AS01疫苗接种水平。相比之下,对照组中没有可测量的抗CSPIgG抗体.
结论:RTS,S/AS01诱导的抗CSPIgG抗体动力学与长寿命但减弱的疫苗效力一致。自然暴露会在儿童中诱导抗CSPIgM抗体,随着年龄的增长,但不会诱导大量的抗CSPIgG抗体。