PDF(Pubmed)
Abstract：
BACKGROUND: RTS,S/AS01, the leading malaria vaccine has been recommended by the WHO for widespread immunization of children at risk. RTS,S/AS01-induced anti-CSP IgG antibodies are associated with the vaccine efficacy. Here, the long-term kinetics of RTS,S/AS01-induced antibodies was investigated.
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.
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.
摘要：
背景：RTS，S/AS01，世卫组织已建议将领先的疟疾疫苗用于高危儿童的广泛免疫接种。RTS,S/AS01诱导的抗CSPIgG抗体与疫苗效力相关。这里,RTS的长期动力学，研究了S/AS01诱导的抗体。
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。
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。
