Toxoplasma gondii GRA15 DNA Vaccine with a Liposomal Nanocarrier Composed of an SS-Cleavable and pH-Activated Lipid-like Material Induces Protective Immunity against Toxoplasmosis in Mice

Tanjila Hasan; Ryo Kawanishi; Hidetaka Akita; Yoshifumi Nishikawa

doi:10.3390/vaccines10010021

Toxoplasma gondii GRA15 DNA Vaccine with a Liposomal Nanocarrier Composed of an SS-Cleavable and pH-Activated Lipid-like Material Induces Protective Immunity against Toxoplasmosis in Mice

Vaccines (Basel). 2021 Dec 24;10(1):21. doi: 10.3390/vaccines10010021.

Authors

Tanjila Hasan^{1

2}, Ryo Kawanishi¹, Hidetaka Akita³, Yoshifumi Nishikawa¹

Affiliations

¹ National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro 080-8555, Hokkaido, Japan.
² Department of Medicine and Surgery, Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University, Khulshi, Chattogram 4225, Bangladesh.
³ Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba City 260-0856, Chiba, Japan.

Abstract

Toxoplasma gondii affects the health of humans and livestock and causes severe illness in the fetus and immunocompromised individuals. Because of the high incidence and severe consequences of T. gondii infection, a safe and suitable vaccine is needed. We found that lipid nanoparticles (LNPs) consisting of a series of functional materials prepared with vitamin E, such as SS-cleavable and pH-activated lipid-like materials (ssPalmE), were a safe and efficient way to develop next-generation DNA vaccines. In this study, we prepared ssPalmE-LNP to encapsulate pCpG-free-T. gondii dense granule protein 15 DNA (ssPalmE-LNP_TgGRA15). Following a challenge infection with avirulent PLK strain of T. gondii, the mice immunized with ssPalmE-LNP_TgGRA15 had a significantly higher survival rate and lower clinical scores compared with unimmunized and ssPalmE-LNP_non-coding-immunized mice. Immunization of mice with the ssPalmE-LNP_TgGRA15 led to a significantly higher production of specific IgG1 and IG2c antibodies compared with unimmunized and ssPalmE-LNP_non-coding-immunized mice, while there was no statistically significant difference in the concentration of serum interferon-gamma at the acute stage of the infection. These findings indicate that ssPalmE-LNP is an effective cargo for the transportation of DNA vaccines for protozoan infections. To explore the mechanism of protective immunity induced by ssPalmE-LNP_TgGRA15, further immunological study is needed in the future.

Keywords: DNA vaccine; TgGRA15; lipid nanoparticle.

Abstract

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