Toxoplasma gondii α-amylase deletion mutant is a promising vaccine against acute and chronic toxoplasmosis.
Toxoplasma gondii α-amylase deletion mutant is a promising vaccine against acute and chronic toxoplasmosis.
复制标题
弓形虫α-淀粉酶缺失突变体是一种有前途的针对急性和慢性弓形虫病的疫苗
DOI：
10.1111/1751-7915.13668
复制
发表时间：
2020-11
影响因子：
5.7
通讯作者：
Fang R
中科院分区：
文献类型：
--
作者：
Yang J;Yang C;Qian J;Li F;Zhao J;Fang R
在研究中，我们首先产生了ME 49 Δα-amy突变体，并发现α-AMY的缺失在体外生长强劲，但导致体内毒力显着减弱。本研究结果表明，ME 49 Δα‐amy弱毒株对急性感染和多株慢性感染均具有较好的免疫保护作用，提示ME 49 Δα‐amy突变株有可能成为一种潜在的疫苗候选株。 免疫力受抑制的个体可能发展为致命的弓形虫病，因此，迫切需要开发安全有效的疫苗。弓形虫（Toxoplasma gondii，T.α-淀粉酶（α-AMY）是负责淀粉消化的酶之一。在本研究中，我们首先产生了ME 49 Δα-amy突变体，并发现α-AMY的缺失在体外稳健生长，但在体内导致显著的毒力衰减。因此，我们建立了小鼠模型，以探讨Δα‐amy突变体对急性和慢性弓形虫病的保护性免疫。结果表明，短期或长期免疫小鼠再次感染多株T.弓形虫感染率接近100%。ME 49 Δα‐amy不仅能提供抗速殖子感染的保护性免疫，而且能抵抗组织包囊的感染。此外，我们检测到ME 49 Δα‐amy疫苗接种可以有效地消除小鼠体内寄生虫的增殖并防止包囊的形成。Th 1型细胞因子、Th 2型细胞因子和特异性总IgG和IgG亚类（IgG 2a和IgG 1）的显著增加证实了细胞和体液免疫组合抗感染的有效性。结论：ME 49 Δα‐amy弱毒株能产生较强的免疫应答，为弓形虫病提供有效的免疫保护，表明ME 49 Δα‐amy突变株可能是一种潜在的疫苗候选株。
In the study, we first generated a ME49Δα‐amy mutant and discovered that loss of α‐AMY robustly grew in vitro but contributed to significant virulence attenuation in vivo. The results obtained from our study revealed that ME49Δα‐amy attenuated strain could provide efficient protection against acute infection and chronic infection caused by multiple strains, which signified that ME49Δα‐amy mutant might be a potential vaccine candidate. Individuals with inhibited immunity may develop lethal toxoplasmosis; thus, a safe and effective vaccine is urged to be developed. Toxoplasma gondii (T. gondii) α‐amylase (α‐AMY) is one of the enzymes responsible for starch digestion. In the present study, we first generated a ME49Δα‐amy mutant and discovered that loss of α‐AMY robustly grew in vitro but contributed to significant virulence attenuation in vivo. Therefore, we established a mouse model to explore the protective immunity of Δα‐amy mutant against acute and chronic toxoplasmosis. The results indicated that the survival rates of short‐term or long‐term immunized mice re‐infected with the tachyzoites of multiple T. gondii strains were nearly 100%. ME49Δα‐amy not only could provide protective immunity against tachyzoites infection but also could resist the infection of tissue cysts. Furthermore, we detected that ME49Δα‐amy vaccination could effectively eliminate the proliferation of parasites in mice and prevent the formation of cysts. The significant increases of Th1‐type cytokines, Th2‐type cytokines and specific total IgG and IgG subclasses (IgG2a and IgG1) confirmed efficiency of a combination of cellular and humoral immunity against infection. In conclusion, ME49Δα‐amy attenuated strain can produce strong immune responses to provide efficient protection against toxoplasmosis, which signifies that ME49Δα‐amy mutant may be a potential vaccine candidate.
登录
查看更多内容
影响因子：
0.6
作者：
Montazeri M;Daryani A;Ebrahimzadeh M;Ahmadpour E;Sharif M;Sarvi S
通讯作者：
Sarvi S
影响因子：
5.2
作者：
Montazeri M;Mehrzadi S;Sharif M;Sarvi S;Tanzifi A;Aghayan SA;Daryani A
通讯作者：
Daryani A
影响因子：
14.2
作者：
Hill, D;Dubey, JP
通讯作者：
Dubey, JP
影响因子：
6.4
作者：
Ismael, Alaa Bassuny;Dimier-Poisson, Isabelle;Mevelec, Marie-Noelle
通讯作者：
Mevelec, Marie-Noelle
影响因子：
28.3
作者：
Di Cristina M;Dou Z;Lunghi M;Kannan G;Huynh MH;McGovern OL;Schultz TL;Schultz AJ;Miller AJ;Hayes BM;van der Linden W;Emiliani C;Bogyo M;Besteiro S;Coppens I;Carruthers VB
通讯作者：
Carruthers VB