Rational Design of a Glycoconjugate Vaccine against Group A Streptococcus.
Rational Design of a Glycoconjugate Vaccine against Group A Streptococcus.
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DOI：
10.3390/ijms21228558
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发表时间：
2020-11-13
影响因子：
5.6
通讯作者：
Micoli F
中科院分区：
文献类型：
--
作者：
Di Benedetto R;Mancini F;Carducci M;Gasperini G;Moriel DG;Saul A;Necchi F;Rappuoli R;Micoli F
A群链球菌是咽炎和脓疱疮的主要病因，在低收入和中等收入国家发生严重后遗症的频率很高，但目前还没有针对它的商业化疫苗。A族碳水化合物（GAC）与合适的载体蛋白结合，被认为是一种有吸引力的候选疫苗。本研究探讨了利用具有抗原和载体双重作用的GAS Streptolysin O （SLO）、SpyCEP和SpyAD蛋白抗原来提高最终疫苗的有效性和降低其复杂性的可能性。所有蛋白抗原都是GAC的良好载体，在小鼠体内诱导与传统的CRM197偶联物相似的抗GAC IgG反应。然而，结合多糖对抗蛋白反应有负面影响，特别是在功能方面，通过IL-8裂解实验和溶血实验对SpyCEP进行了评估。在选择CRM197作为载体后，通过实验设计方法确定了其与GAC结合的最佳条件，提高了工艺稳健性和产率。这项工作支持针对GAS的疫苗的开发，并展示了新的统计工具和缀合领域的最新进展如何导致改进糖缀合疫苗的设计。
No commercial vaccine is yet available against Group A Streptococcus (GAS), major cause of pharyngitis and impetigo, with a high frequency of serious sequelae in low- and middle-income countries. Group A Carbohydrate (GAC), conjugated to an appropriate carrier protein, has been proposed as an attractive vaccine candidate. Here, we explored the possibility to use GAS Streptolysin O (SLO), SpyCEP and SpyAD protein antigens with dual role of antigen and carrier, to enhance the efficacy of the final vaccine and reduce its complexity. All protein antigens resulted good carrier for GAC, inducing similar anti-GAC IgG response to the more traditional CRM197 conjugate in mice. However, conjugation to the polysaccharide had a negative impact on the anti-protein responses, especially in terms of functionality as evaluated by an IL-8 cleavage assay for SpyCEP and a hemolysis assay for SLO. After selecting CRM197 as carrier, optimal conditions for its conjugation to GAC were identified through a Design of Experiment approach, improving process robustness and yield This work supports the development of a vaccine against GAS and shows how novel statistical tools and recent advancements in the field of conjugation can lead to improved design of glycoconjugate vaccines.
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