Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis.
Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis.
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DOI：
10.1016/s2666-5247(21)00267-6
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发表时间：
2022-01
期刊：
影响因子：
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通讯作者：
Davenport MP
中科院分区：
文献类型：
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作者：
Cromer D;Steain M;Reynaldi A;Schlub TE;Wheatley AK;Juno JA;Kent SJ;Triccas JA;Khoury DS;Davenport MP
已经确定了几种令人担忧的SARS-CoV-2变体，它们部分逃避了当前疫苗引起的血清中和。研究还表明，疫苗对SARS-CoV-2变异体症状感染的保护作用降低。我们探讨了体外中和滴度是否仍然预测疫苗对SARS-CoV-2变异体感染的保护作用。在这项荟萃分析中，我们分析了来自24项体外中和和临床保护研究的已发表数据，以了解对现有SARS-CoV-2变异株的中和损失。我们将该分析的结果整合到我们现有的将体外中和与保护相关联的统计模型中（根据祖先病毒感染的数据进行参数化），以估计疫苗对SARS-CoV-2变体的有效性。我们还分析了加强疫苗应答的数据，并使用该模型预测加强疫苗接种对SARS-CoV-2变异体保护的影响。对祖先SARS-CoV-2的中和活性高度预测了所关注变体的中和。不同疫苗之间α（1.6倍）、β（8.8倍）、γ（3.5倍）和δ（3.9倍）变体（与祖先病毒相比）的中和滴度降低无显著差异。中和作用仍然与预防SARS-CoV-2相关变异体的症状性感染密切相关（rS= 0.81，p= 0.0005），并且一旦纳入对相关变异体的中和作用降低，现有模型仍然可以预测疫苗对相关变异体的有效性。随着时间的推移，预测疫苗对变异体的有效性的建模表明，对症状性感染的保护可能在接种某些疫苗后的第一年内下降到50%以下。预测用现有疫苗（其靶向祖先病毒）加强先前感染的个体比单独的初级疫苗接种计划提供更高程度的保护以免受关注变体的感染。体外中和滴度仍然与SARS-CoV-2变体的保护相关，并且免疫力减弱的影响模型预测了疫苗接种后对变体的保护丧失。然而，与初次接种相比，使用当前疫苗的加强接种应能够实现对SARS-CoV-2变体的更高中和，预计至少在中期内，对于当前关注的SARS-CoV-2变体的严重感染结果提供稳健的保护。国家健康和医学研究理事会（澳大利亚）、医学研究未来基金（澳大利亚）和维多利亚州政府。
Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants. In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants. The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (rS=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone. In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term. The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.