Design of a Glycoconjugate Vaccine Against Salmonella Paratyphi A.

IF 5.2 3区医学 Q1 IMMUNOLOGY

Vaccines Pub Date : 2024-11-12 DOI:10.3390/vaccines12111272

Renzo Alfini, Martina Carducci, Luisa Massai, Daniele De Simone, Marco Mariti, Omar Rossi, Simona Rondini, Francesca Micoli, Carlo Giannelli

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引用次数: 0

Abstract

Background/objectives: Typhoid and paratyphoid fever together are responsible for millions of cases and thousands of deaths per year, most of which occur in children in South and Southeast Asia. While typhoid conjugate vaccines (TCVs) are licensed, no vaccines are currently available against S. Paratyphi A. Here we describe the design of a S. Paratyphi A conjugate.

Methods: The serovar-specific O-antigen (O:2) was linked to the CRM₁₉₇ carrier protein (O:2-CRM₁₉₇) and a panel of conjugates differing for structural characteristics were compared in mice and rabbits.

Results: We identified the O-antigen molecular size, polysaccharide to protein ratio, conjugate cross-linking, and O:2 O-acetylation level as critical quality attributes and identified optimal design for a more immunogenic vaccine.

Conclusions: This work guides the development of the O:2-CRM₁₉₇ conjugate to be combined with TCV in a bivalent formulation against enteric fever.

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设计一种针对 A 型副伤寒沙门氏菌的糖结合疫苗

背景/目标：伤寒和副伤寒每年导致数百万例病例和数千人死亡，其中大部分发生在南亚和东南亚地区的儿童身上。虽然伤寒结合疫苗（TCV）已获得许可，但目前还没有针对 A 型副伤寒的疫苗：方法：将血清特异性 O 抗原（O:2）与 CRM197 载体蛋白（O:2-CRM197）连接，并在小鼠和兔子体内比较了一系列结构特征不同的共轭物：结果：我们确定了O型抗原分子大小、多糖与蛋白质比例、共轭物交联和O:2 O-乙酰化水平是关键的质量属性，并确定了更高免疫原性疫苗的最佳设计：这项研究为开发 O:2-CRM197 结合体与 TCV 结合的二价肠道热疫苗配方提供了指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vaccines Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

8.90

自引率

16.70%

发文量

1853

审稿时长

18.06 days

期刊介绍： Vaccines (ISSN 2076-393X) is an international, peer-reviewed open access journal focused on laboratory and clinical vaccine research, utilization and immunization. Vaccines publishes high quality reviews, regular research papers, communications and case reports.