Development of a synthetic Vi polysaccharide vaccine for typhoid fever.
Development of a synthetic Vi polysaccharide vaccine for typhoid fever.
复制标题
开发伤寒合成 Vi 多糖疫苗。
DOI：
10.1016/j.vaccine.2017.10.081
复制
发表时间：
2017
期刊：
影响因子：
5.5
通讯作者：
Tizard,Ian
中科院分区：
文献类型：
--
作者：
Ni,Yawei;Springer,MichaelJ;Guo,Jianhua;Finger-Baker,Isaac;Wilson,JamesP;Cobb,RonaldR;Turner,Debra;Tizard,Ian
伤寒仍然是一个严重的公共卫生问题，对幼儿和幼儿的影响很大。针对Vi荚膜多糖的疫苗对伤寒有效，证明针对Vi的抗体赋予保护作用。然而，目前许可的Vi伤寒疫苗具有有限的效力，并且通过复杂的过程从野生型细菌制造。由于当前疫苗的这些固有问题，产生了基于0-乙酰化高分子量（HMW）聚半乳糖醛酸（GelSite-OAcTM）的替代疫苗。高分子量聚半乳糖醛酸与伤寒沙门氏菌Vi多糖具有相同的骨架。GelSite-OAcTM具有高分子量（>1 × 106 Da）和高O-乙酰化度（DOAc）（>5 μmole/mg），均超过当前Vi疫苗的效力规格。在Balb/c小鼠中的研究表明，GelSite-OAcTM具有高度免疫原性，以DOAc和剂量依赖性方式诱导强烈的抗原特异性抗体应答，其与许可的Vi疫苗诱导的应答相当或更高。重要的是，GelSite-OAcTM在小鼠中显示出对伤寒沙门氏菌致死性攻击的完全保护作用。此外，GelSite-OAcTM表现出增强效应或记忆反应，在使用GelSite-OAcTM或Vi疫苗进行第二次免疫后，抗体水平增加>2倍。这种新的加强作用在多糖抗原中是独特的，并可能使GelSite-OAc™对2岁以下的人有效。这些结果共同表明，GelSite-OAcTM可能是一种针对伤寒沙门氏菌的高效疫苗。
Typhoid fever remains a serious public health problem with a high impact on toddlers and young children. Vaccines against the Vi capsular polysaccharide are efficacious against typhoid fever demonstrating that antibodies against Vi confer protection. The currently licensed Vi typhoid vaccines have however limited efficacy and are manufactured by a complex process from wild-type bacteria. Due to these inherent issues with the current vaccines, an alternative vaccine based on an O-acetylated high molecular weight (HMW) polygalacturonic acid (GelSite-OAc™) was generated. The HMW polygalacturonic acid shares the same backbone as the Vi polysaccharide ofSalmonellaTyphi. The GelSite-OAc™ has a high molecular weight (>1 × 106Da) and a high degree of O-acetylation (DOAc) (>5 μmole/mg), both exceeding the potency specifications of the current Vi vaccine. Studies in Balb/c mice demonstrated that GelSite-OAc™ was highly immunogenic, inducing a strong antigen-specific antibody response in a DOAc- and dose-dependent manner which was comparable to or higher than those induced by the licensed Vi vaccine. Importantly, the GelSite-OAc™ was shown to be fully protective in mice against lethal challenge withSalmonellaTyphi. Furthermore, the GelSite-OAc™ demonstrated a boosting effect or memory response, exhibiting a >2-fold increase in antibody levels upon the second immunization with either GelSite-OAc™ or the Vi vaccine. This novel boosting effect is unique among polysaccharide antigens and potentially makes GelSite-OAc™ effective in people under 2 years old. Together these results suggest that the GelSite-OAc™ could be a highly effective vaccine againstSalmonellaTyphi.
登录
查看更多内容
影响因子：
5.5
作者：
Velasquez, Lissette S.;Shira, Samantha;Berta, Alice N.;Kilbourne, Jacquelyn;Medi, Babu M.;Tizard, Ian;Ni, Yawei;Arntzen, Charles J.;Herbst-Kralovetz, Melissa M.
通讯作者：
Herbst-Kralovetz, Melissa M.
影响因子：
5.5
作者：
Kariuki S;Gordon MA;Feasey N;Parry CM
通讯作者：
Parry CM
O-乙酰果胶 [poly(1-->4)-alpha-D-GalpA]-蛋白缀合物作为伤寒疫苗的合成和一些免疫学特性
影响因子：
3.1
作者：
S. Szu;S. Bystrický;M. Hinojosa;W. Egan;J. Robbins
通讯作者：
J. Robbins
将伤寒疫苗接种纳入全球卫生议程。
影响因子：
158.5
作者：
D. Deroeck;L. Jodar;J. Clemens
通讯作者：
J. Clemens
DOI：
10.1086/649541
发表时间：
2010-01-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Crump JA;Mintz ED
通讯作者：
Mintz ED