SARS-CoV-2 刺突抗体水平向人群免疫基准点收敛。

Convergence of SARS-CoV-2 spike antibody levels to a population immune setpoint.

机构信息

Brigham and Womens Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Harvard Humanitarian Initiative, Cambridge, MA, USA.

Brigham and Womens Hospital, Boston, MA, USA; Harvard Humanitarian Initiative, Cambridge, MA, USA.

出版信息

EBioMedicine. 2024 Oct;108:105319. doi: 10.1016/j.ebiom.2024.105319. Epub 2024 Sep 3.

DOI:10.1016/j.ebiom.2024.105319

PMID:39232463

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11404201/

Abstract

BACKGROUND

Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications.

METHODS

We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes.

FINDINGS

We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile.

INTERPRETATION

Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens.

FUNDING

The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL).

摘要

背景

人们对 SARS-CoV-2 的个体免疫反应进行了深入研究，而这些反应对人群免疫动态的综合影响仍知之甚少。鉴于人群免疫力对病原体传播的关键作用，明确驱动人群免疫进化的因素具有重要的公共卫生意义。

方法

我们在多米尼加共和国的西北部和东南部采用多阶段聚类调查方法招募了 5 岁及以上的个体。在大流行中期（2021 年 8 月）和大流行后期（2022 年 11 月）采集了配对的血样。我们测量了针对 SARS-CoV-2 刺突蛋白的血清泛免疫球蛋白抗体。广义加性模型（GAMs）和随机森林模型用于分析抗体水平变化与各种预测变量之间的关系。主成分分析和部分依赖图进一步探讨了预测因子与抗体变化之间的关系。