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

Front Cell Infect Microbiol. 2023 Jul 12:13:1209755. doi: 10.3389/fcimb.2023.1209755. eCollection 2023.

Abstract

Background: Toxoplasma gondii is an apicomplexan parasite that affects the health of humans and livestock, and an effective vaccine is urgently required. Nanoparticles can modulate and improve cellular and humoral immune responses.

Methods: In the current study, poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles were used as a delivery system for the T. gondii dense granule antigens GRA12 and GRA7. BALB/c mice were injected with the vaccines and protective efficacy was evaluated.

Results: Mice immunized with PLGA+GRA12 exhibited significantly higher IgG, and a noticeable predominance of IgG2a over IgG1 was also observed. There was a 1.5-fold higher level of lymphocyte proliferation in PLGA+GRA12-injected mice compared to Alum+GRA12-immunized mice. Higher levels of IFN-g and IL-10 and a lower level of IL-4 were detected, indicating that Th1 and Th2 immune responses were induced but the predominant response was Th1. There were no significant differences between Alum+GRA7-immunized and PLGA+GRA7-immunized groups. Immunization with these four vaccines resulted in significantly reduced parasite loads, but they were lowest in PLGA+GRA12-immunized mice. The survival times of mice immunized with PLGA+GRA12 were also significantly longer than those of mice in the other vaccinated groups.

Conclusion: The current study indicated that T. gondii GRA12 recombinant protein encapsulated in PLGA nanoparticles is a promising vaccine against acute toxoplasmosis, but PLGA is almost useless for enhancing the immune response induced by T. gondii GRA7 recombinant protein.

Keywords: GRA12; GRA7; PLGA; Toxoplasma gondii; nanoparticles; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan
  • Antigens, Protozoan / genetics
  • Humans
  • Lactic Acid
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles*
  • Protozoan Proteins / genetics
  • Protozoan Vaccines*
  • Recombinant Proteins
  • Toxoplasma*
  • Toxoplasmosis*

Substances

  • aluminum sulfate
  • Protozoan Proteins
  • Antigens, Protozoan
  • Recombinant Proteins
  • Lactic Acid
  • Protozoan Vaccines
  • Antibodies, Protozoan

Grants and funding

This work was supported by the National Natural Science Foundation of China (31802183, 32072883), Zhejiang Province “Sannongjiufang” Science and Technology Cooperation Project (2023SNJF059), Hangzhou Agricultural and Social Development Project (202203B19), Hangzhou Science and Technology Commissioner Project (20211122I30), and International Cooperation Projects of Zhejiang Academy of Agricultural Sciences.