Anti-circumsporozoite antibody titres have been established as an essential indicator for evaluating the immunogenicity and protective capacity of the RTS,S/AS01 malaria vaccine. However, a new delayed-fractional dose regime of the vaccine was recently shown to increase vaccine efficacy, from 62.5% (95% CI 29.4–80.1%) under the original dosing schedule to 86.7% (95% CI, 66.8–94.6%) without a corresponding increase in antibody titres. Here we reanalyse the antibody data from this challenge trial to determine whether IgG avidity may help to explain efficacy better than IgG titre alone by adapting a within-host mathematical model of sporozoite inoculation. We demonstrate that a model incorporating titre and avidity provides a substantially better fit to the data than titre alone. These results also suggest that in individuals with a high antibody titre response that also show high avidity (both metrics in the top tercile of observed values) delayed-fractional vaccination provided near perfect protection upon first challenge (98.2% [95% Credible Interval 91.6–99.7%]). This finding suggests that the quality of the vaccine induced antibody response is likely to be an important determinant in the development of highly efficacious pre-erythrocytic vaccines against malaria.

已经建立了抗环子孢子抗体滴度，作为评估RTS，S / AS01疟疾疫苗的免疫原性和保护能力的重要指标。但是，最近显示出一种新的延迟分次剂量方案可以提高疫苗效力，从原始给药方案的62.5％（95％CI 29.4–80.1％）提高到86.7％（95％CI，66.8–94.6％）没有相应的抗体滴度增加。在这里，我们重新分析来自该挑战试验的抗体数据，以确定是否通过适应宿主内子孢子接种的数学模型，IgG亲和力是否可以比单独使用IgG滴度更好地解释功效。我们证明，结合了效价和亲和力的模型比单独的效价提供了更好的数据拟合性。这些结果还表明，在具有高抗体滴度反应且也显示出高亲和力的个人中（这两个指标均在观察到的值的最高位），延迟分次疫苗接种在首次攻击时提供了近乎完美的保护（98.2％[95％可信区间91.6– 99.7％]）。该发现表明，疫苗诱导的抗体应答的质量可能是开发抗疟疾的高效促红细胞生成前疫苗的重要决定因素。