PDF(Pubmed)
Abstract：
BACKGROUND: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group.
METHODS: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01.
RESULTS: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series.
CONCLUSIONS: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.
METHODS: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01.
RESULTS: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series.
CONCLUSIONS: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.
摘要：
背景：RTS，世卫组织已建议在中高疟疾传播环境中广泛实施S/AS01。先前的分析指出，在较高的传播环境中，疫苗的效力较低，可能是由于对照组的自然获得性免疫发展更快。
方法：为了研究疫苗接种后免疫反应的降低，作为高传播地区疗效降低的潜在机制，我们使用来自三个研究领域的数据（Kintampo，加纳；利隆圭，马拉维；Lambaréné,加蓬）来自2009-2014年III期试验（NCT00866619）。我们的主要暴露是疫苗接种系列期间的寄生虫血症和背景疟疾发病率。我们使用cox比例风险模型并考虑RTS的时变效应来计算疫苗效力（1减去风险比），S/AS01。
结果：我们发现，加纳对主要三剂量疫苗系列的抗体反应高于马拉维和加蓬，但是在初级疫苗接种系列中，针对第一例疟疾的抗体水平和疫苗效力都不因背景发病率或寄生虫血症而异。
结论：我们发现疫苗效力与疫苗接种期间的感染无关。促成了一个相互矛盾的文学，我们的结果表明，疫苗效力也与疫苗接种前的感染无关，这意味着对照组免疫力可能是高传播环境中疗效较低的主要原因，不减少对RTS的免疫反应，S/AS01。这对于在高传输设置中的实施可能是令人放心的，虽然还需要进一步的研究。
方法：为了研究疫苗接种后免疫反应的降低，作为高传播地区疗效降低的潜在机制，我们使用来自三个研究领域的数据（Kintampo，加纳；利隆圭，马拉维；Lambaréné,加蓬）来自2009-2014年III期试验（NCT00866619）。我们的主要暴露是疫苗接种系列期间的寄生虫血症和背景疟疾发病率。我们使用cox比例风险模型并考虑RTS的时变效应来计算疫苗效力（1减去风险比），S/AS01。
结果：我们发现，加纳对主要三剂量疫苗系列的抗体反应高于马拉维和加蓬，但是在初级疫苗接种系列中，针对第一例疟疾的抗体水平和疫苗效力都不因背景发病率或寄生虫血症而异。
结论：我们发现疫苗效力与疫苗接种期间的感染无关。促成了一个相互矛盾的文学，我们的结果表明，疫苗效力也与疫苗接种前的感染无关，这意味着对照组免疫力可能是高传播环境中疗效较低的主要原因，不减少对RTS的免疫反应，S/AS01。这对于在高传输设置中的实施可能是令人放心的，虽然还需要进一步的研究。
