The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi.
The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi.
复制标题
DOI：
10.1371/journal.pone.0189100
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Micoli F
中科院分区：
文献类型：
--
作者：
Arcuri M;Di Benedetto R;Cunningham AF;Saul A;MacLennan CA;Micoli F
近年来，人们在开发以多糖为基础的糖结合疫苗方面做出了重大努力，这些疫苗将预防伤寒沙门氏菌感染，特别是伤寒，这仍然是低收入国家的一个主要公共卫生问题。糖结合疫苗的设计影响其引发的免疫反应。在这里，我们系统地测试了小鼠对不同Vi链长度（全长和片段化）、载体蛋白、偶联化学、糖蛋白比和大小的Vi糖缀合物的反应。我们发现，Vi链的长度，而不是缀合物的最终大小，对诱导的抗Vi IgG免疫反应有影响。全长Vi偶联物独立于载体蛋白，在一次免疫后迅速诱导IgG应答峰值，而二次免疫并不会增强这些应答的强度。与CRM197和白喉类毒素（而非破伤风类毒素）结合的片段性Vi在第一次免疫后产生的抗Vi抗体应答低于全长Vi偶联物，但抗体效价与第二次接种后由全长Vi偶联物诱导的抗体效价相似。将Vi与载体蛋白结合的化学过程、所使用的连接剂以及糖与蛋白质的比例都不会显著改变反应。我们认为，影响抗-Vi IgG免疫应答的变量是病毒长度和载体蛋白，而其他参数的影响较小。
In recent years there have been major efforts to develop glycoconjugate vaccines based on the Vi polysaccharide that will protect against Salmonella enterica Typhi infections, particularly typhoid fever, which remains a major public health concern in low-income countries. The design of glycoconjugate vaccines influences the immune responses they elicit. Here we systematically test the response in mice to Vi glycoconjugates that differ in Vi chain length (full-length and fragmented), carrier protein, conjugation chemistry, saccharide to protein ratio and size. We show that the length of Vi chains, but not the ultimate size of the conjugate, has an impact on the anti-Vi IgG immune response induced. Full-length Vi conjugates, independent of the carrier protein, induce peak IgG responses rapidly after just one immunization, and secondary immunization does not enhance the magnitude of these responses. Fragmented Vi linked to CRM197 and diphtheria toxoid, but not to tetanus toxoid, gives lower anti-Vi antibody responses after the first immunization than full-length Vi conjugates, but antibody titres are similar to those induced by full-length Vi conjugates following a second dose. The chemistry to conjugate Vi to the carrier protein, the linker used, and the saccharide to protein ratio do not significantly alter the response. We conclude that Vi length and carrier protein are the variables that influence the anti-Vi IgG response to immunization the most, while other parameters are of lesser importance.
登录
查看更多内容
影响因子：
6.8
作者：
Lebacq, E
通讯作者：
Lebacq, E
影响因子：
3
作者：
Chibber, S;Bhardwaj, SB
通讯作者：
Bhardwaj, SB
影响因子：
5.5
作者：
Micoli, F.;Rondini, S.;Martin, L. B.
通讯作者：
Martin, L. B.
影响因子：
3.1
作者：
Kossaczka, Z;Lin, FYC;Szu, SC
通讯作者：
Szu, SC
影响因子：
4.8
作者：
MacLennan CA;Martin LB;Micoli F
通讯作者：
Micoli F