An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats

被引：105

作者：

Ramakrishnan, Chandra ^{[1
]}

Maier, Simone ^{[1
]}

Walker, Robert A. ^{[1
]}

Rehrauer, Hubert ^{[2
]}

Joekel, Deborah E. ^{[1
]}

Winiger, Rahel R. ^{[1
]}

Basso, Walter U. ^{[1
]}

Grigg, Michael E. ^{[3
]}

Hehl, Adrian B. ^{[1
]}

Deplazes, Peter ^{[1
]}

Smith, Nicholas C. ^{[4
,5
]}

机构：

[1] Univ Zurich, Inst Parasitol, Winterthurerstr 266a, CH-8057 Zurich, Switzerland

[2] Funct Genom Ctr Zurich, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[3] NIAID, Mol Parasitol Sect, Lab Parasit Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[4] Australian Natl Univ, Res Sch Biol, Canberra, ACT 0200, Australia

[5] Univ Western Sydney, Sch Sci & Hlth, Parramatta South Campus, Sydney, NSW 2116, Australia

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

T-263; STRAIN; OOCYST WALL; EIMERIA; PROTEIN; TENELLA; GENE; EXPRESSION; RESISTANCE; APICOPLAST; DEFICIENT;

D O I：

10.1038/s41598-018-37671-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Almost any warm-blooded creature can be an intermediate host for Toxoplasma gondii. However, sexual reproduction of T. gondii occurs only in felids, wherein fertilisation of haploid macrogametes by haploid microgametes, results in diploid zygotes, around which a protective wall develops, forming unsporulated oocysts. Unsporulated oocysts are shed in the faeces of cats and meiosis gives rise to haploid sporozoites within the oocysts. These, now infectious, sporulated oocysts contaminate the environment as a source of infection for people and their livestock. RNA-Seq analysis of cat enteric stages of T. gondii uncovered genes expressed uniquely in microgametes and macrogametes. A CRISPR/Cas9 strategy was used to create a T. gondii strain that exhibits defective fertilisation, decreased fecundity and generates oocysts that fail to produce sporozoites. Inoculation of cats with this engineered parasite strain totally prevented oocyst excretion following infection with wild-type T. gondii, demonstrating that this mutant is an attenuated, live, transmission-blocking vaccine.

引用

页数：14

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