Modulation Effects of Toxoplasma gondii Histone H2A1 on Murine Macrophages and Encapsulation with Polymer as a Vaccine Candidate

Abstract

Toxoplasma gondii (T. gondii) is the most common zoonotic protozoa and has infected about one-third of the population worldwide. Recombinant epitopes encapsulated in nanospheres have advantages over traditional T. gondii vaccines. For an efficient delivery system, poly (DL-lactide-co-glycolide) (PLGA) and chitosan are the most frequently used biodegradable polymeric nanospheres with strong safety profiles. In the present study, we first expressed and purified histone H2A1 of T. gondii using the prokaryotic expression system. The effects of recombinant TgH2A1 on the functions of murine macrophages were then studied. Purified recombinant TgH2A1 was then encapsulated in nanospheres with PLGA and chitosan. After subcutaneous vaccination in mice, the immune response was evaluated by double antibody sandwich ELISA kits. The results from this study showed that PLGA and chitosan loaded with rTgH2A1 could trigger a stronger Th1 oriented immune response and prolong the survival time of mice effectively. In conclusion, PLGA and chitosan nanospheres loaded with histone H2A1 are an effective method for the development of vaccines against T. gondii. Further studies should focus on evaluating the regulatory mechanism of TgH2A1, vaccine potency, and cellular response in chronic T. gondii infections.

Protective efficacy of Toxoplasma gondii GRA12 or GRA7 recombinant proteins encapsulated in PLGA nanoparticles against acute Toxoplasma gondii infection in mice

“…Survival rates in the Alum+GRA7, PLGA+GRA7, and Alum+GRA12 groups were lower than that in the PLGA+GRA12 group, and significantly prolonged survival was evident in the PLGA+GRA12 group. In a previous study, mice vaccinated with rTgH2A1/PLGA exhibited a significantly increased survival time ( Yu et al., 2020 ). In future experiments, it would be informative to evaluate the immune protection induced by PLGA+GRA12 in low-virulence T. gondii strains.…”

Study on Circulating Antigens in Serum of Mice With Experimental Acute Toxoplasmosis

“…Most CAgs are ESA that play important roles in inducing appropriate humoral and cellular immune responses against T. gondii ( Hafid et al, 2005 ; Jongert et al, 2009 ; Costa-Silva et al, 2012 ; Chen et al, 2013 ; Daryani et al, 2014 ). Moreover, some proteins identified herein such as PLP1 ( Yan et al, 2011 ), M2AP ( Dautu et al, 2007 ), SAG1 ( Mohamed et al, 2003 ), protease inhibitor PI1 ( Cuppari et al, 2008 ), Histone H2A ( Yu et al, 2020 ), Elongation factor 1-alpha (EF-1α; Wang et al, 2017 ), CDPK9 ( Wang H. L. et al, 2016 ; Wang J. L. et al, 2016 ), HSP70 ( Mohamed et al, 2003 ), protein disulfide-isomerase ( Wang et al, 2013 ), and toxofilin ( Song et al, 2017 ) elicit powerful specific immune responses, providing partial protection against acute or chronic T. gondii infection. Thus, we evaluated the protective ability of TgRuvBL1, TgRNase H1, and TgRPS2.…”

Nanoparticles as a Delivery System of Antigens for the Development of an Effective Vaccine against Toxoplasma gondii

“…Mice immunized with porous NPs containing TE have been shown to induce a Th1/Th17 immune response able to prolong mouse survival and drastically reduce brain cyst counts [91]. Polymeric NPs loaded with T. gondii histone H2A1 conferred mice with protection against infection, prolonging their survival and the production of Th1 cytokines [92]. A similar study using PLGA NPs containing T and B cell epitopes of AMA1, GRA4, ROP2, and SAG1, adjuvanted with potassium Alum sulphate, induced a stronger Th1 immune response in mice, compared to immunization solely with antigens [93].…”