Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine Model

Toxoplasmosis is a serious zoonotic disease that threatens human and animal health. Here, we evaluated the vaccine potential of the deletion of <i>Toxoplasma</i> rhoptry protein 38 (PruΔ<i>rop38</i>) through its pathogenicity and immunoprotective efficacy in mice. Mice inocul...

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Main Authors: Yayun Wu, Zihui Zhou, Zhu Ying, Ying Xu, Jing Liu, Qun Liu
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/6/1336
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author Yayun Wu
Zihui Zhou
Zhu Ying
Ying Xu
Jing Liu
Qun Liu
author_facet Yayun Wu
Zihui Zhou
Zhu Ying
Ying Xu
Jing Liu
Qun Liu
author_sort Yayun Wu
collection DOAJ
description Toxoplasmosis is a serious zoonotic disease that threatens human and animal health. Here, we evaluated the vaccine potential of the deletion of <i>Toxoplasma</i> rhoptry protein 38 (PruΔ<i>rop38</i>) through its pathogenicity and immunoprotective efficacy in mice. Mice inoculated intraperitoneally with 1 × 10<sup>3</sup>, 2 × 10<sup>3</sup>, or 4 × 10<sup>3</sup> PruΔ<i>rop38</i> showed no visible signs, whereas mice inoculated with 1 × 10<sup>3</sup> parental Pru strain showed obvious wasting and bow-back, suggesting a significantly lower pathogenicity of PruΔ<i>rop38</i> in mice. Vaccination with 1 × 10<sup>2</sup> PruΔ<i>rop38</i> triggered a mixed Th1/Th2 response (Th1 response predominant), with higher IgG, IgG2a, and IgG1 levels in serum from week 3 to week 12, and a significant increase in IFN-γ, IL-12, and IL-10 in suspensions of splenocytes at 30 or 60 days post-immunization. All vaccinated mice survived when infected intraperitoneally with tachyzoites (RH, Pru, VEG, or TgcatBJ1) or when infected orally with cysts (Pru or ME49). The brain parasite burden during Pru tachyzoite, Pru cyst and ME49 cyst challenges were significantly reduced in vaccinated mice. The duration of immunization showed that vaccination with PruΔ<i>rop38</i> could protect mice from challenge with different varied genotypes of <i>Toxoplasma</i> strains against different routes of infection. Collectively, these findings indicate that PruΔ<i>rop38</i> is an attenuated strain that provides long-term protective efficacy against acute or chronic toxoplasmosis in mice.
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spelling doaj.art-2b2d93a695854e72aea56356a187cefe2023-11-23T15:43:00ZengMDPI AGBiomedicines2227-90592022-06-01106133610.3390/biomedicines10061336Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine ModelYayun Wu0Zihui Zhou1Zhu Ying2Ying Xu3Jing Liu4Qun Liu5National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaToxoplasmosis is a serious zoonotic disease that threatens human and animal health. Here, we evaluated the vaccine potential of the deletion of <i>Toxoplasma</i> rhoptry protein 38 (PruΔ<i>rop38</i>) through its pathogenicity and immunoprotective efficacy in mice. Mice inoculated intraperitoneally with 1 × 10<sup>3</sup>, 2 × 10<sup>3</sup>, or 4 × 10<sup>3</sup> PruΔ<i>rop38</i> showed no visible signs, whereas mice inoculated with 1 × 10<sup>3</sup> parental Pru strain showed obvious wasting and bow-back, suggesting a significantly lower pathogenicity of PruΔ<i>rop38</i> in mice. Vaccination with 1 × 10<sup>2</sup> PruΔ<i>rop38</i> triggered a mixed Th1/Th2 response (Th1 response predominant), with higher IgG, IgG2a, and IgG1 levels in serum from week 3 to week 12, and a significant increase in IFN-γ, IL-12, and IL-10 in suspensions of splenocytes at 30 or 60 days post-immunization. All vaccinated mice survived when infected intraperitoneally with tachyzoites (RH, Pru, VEG, or TgcatBJ1) or when infected orally with cysts (Pru or ME49). The brain parasite burden during Pru tachyzoite, Pru cyst and ME49 cyst challenges were significantly reduced in vaccinated mice. The duration of immunization showed that vaccination with PruΔ<i>rop38</i> could protect mice from challenge with different varied genotypes of <i>Toxoplasma</i> strains against different routes of infection. Collectively, these findings indicate that PruΔ<i>rop38</i> is an attenuated strain that provides long-term protective efficacy against acute or chronic toxoplasmosis in mice.https://www.mdpi.com/2227-9059/10/6/1336toxoplasmosisPruΔ<i>rop38</i>pathogenicityprotective efficacymice
spellingShingle Yayun Wu
Zihui Zhou
Zhu Ying
Ying Xu
Jing Liu
Qun Liu
Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine Model
Biomedicines
toxoplasmosis
PruΔ<i>rop38</i>
pathogenicity
protective efficacy
mice
title Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine Model
title_full Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine Model
title_fullStr Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine Model
title_full_unstemmed Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine Model
title_short Deletion of <i>Toxoplasma</i> Rhoptry Protein 38 (PruΔ<i>rop38</i>) as a Vaccine Candidate for Toxoplasmosis in a Murine Model
title_sort deletion of i toxoplasma i rhoptry protein 38 pruδ i rop38 i as a vaccine candidate for toxoplasmosis in a murine model
topic toxoplasmosis
PruΔ<i>rop38</i>
pathogenicity
protective efficacy
mice
url https://www.mdpi.com/2227-9059/10/6/1336
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