Applying mathematical tools to accelerate vaccine development: modeling Shigella immune dynamics.
Applying mathematical tools to accelerate vaccine development: modeling Shigella immune dynamics.
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DOI：
10.1371/journal.pone.0059465
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Levy D
中科院分区：
文献类型：
--
作者：
Davis CL;Wahid R;Toapanta FR;Simon JK;Sztein MB;Levy D
我们建立了一个数学框架来研究志贺氏菌的免疫相互作用，志贺氏菌是一种每年导致全世界超过一百万人死亡的细菌。这种新方法的长期目标是通过阐明哪些免疫成分和细菌靶标对于建立志贺氏菌免疫力至关重要，为志贺氏菌疫苗设计提供信息。我们的延迟微分方程模型重点关注针对志贺氏菌外膜中的脂多糖等抗原的抗体和 B 细胞反应。我们发现仅针对表面抗原的基于抗体的疫苗不能引起足够的免疫保护。感染前的额外加强将需要抗体增加四个数量级才能充分防止上皮侵袭。然而，增强抗 LPS B 记忆可以提供保护，这表明这些细胞可能与免疫相关。我们发现 IgA 抗体的每个分子比 IgG 稍微更有效，但由于空间功能，需要更多的总 IgA。该模型的扩展表明，针对 LPS 和上皮进入蛋白是推进疫苗开发的一条有希望的途径。本文强调了多方面免疫靶向在创造有效志贺氏菌疫苗中的重要性。它为志贺氏菌疫苗开发工作引入了数学模型，并为志贺氏菌疫苗设计的联合理论/实验/临床方法奠定了基础。
We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella’s outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design.
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