Protective mucosal and systemic immunity induced by virus-like particles expressing Toxoplasma gondii cyst wall protein

PLoS One. 2023 Apr 27;18(4):e0283928. doi: 10.1371/journal.pone.0283928. eCollection 2023.

Abstract

Toxoplasma gondii host cellular invasion factors such as the rhoptry proteins, micronemal antigens, or other subcellular compartment proteins have shown limited vaccine efficacies. T. gondii cyst wall protein (CST1) as a cyst persistence factor is critical for cyst wall integrity and bradyzoite persistence. Here, we generated influenza virus-like particles (VLPs) expressing the T. gondii CST1 and evaluated the mucosal as well as systemic immunities induced by VLPs. Intranasal immunization with the VLPs induced parasite-specific IgG and IgA antibody responses in sera and intestines. VLP immunization showed higher levels of germinal center B cell response and antibody-secreting cell (ASC) response upon challenge infection, indicating memory B cell response was induced. VLP-immunized mice showed a significant reduction of cyst counts and lower levels of pro-inflammatory cytokines (IFN-γ, IL-6) production in the brain upon T. gondii ME49 challenge infection compared to unimmunized control. Thus, VLP immunization protected mice from the lethal dose challenge infection with T. gondii ME49 and did not incur bodyweight loss. These results indicated that T. gondii CST1 containing VLPs can induce mucosal and systemic immunity and also suggest its developmental potential as an effective vaccine candidate against T. gondii infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan
  • Cytokines
  • Immunity, Mucosal
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins
  • Protozoan Vaccines*
  • Toxoplasma*
  • Vaccination
  • Vaccines, Virus-Like Particle*

Substances

  • Protozoan Proteins
  • Protozoan Vaccines
  • Vaccines, Virus-Like Particle
  • Cytokines
  • Antibodies, Protozoan

Grants and funding

F.S.Q. - National Research Foundation of Korea (NRF) (2018R1A6A1A03025124) F.S.Q. - Ministry of Health & Welfare, Republic of Korea (HV20C0085). F.S.Q. - Ministry of Health & Welfare, Republic of Korea (HV20C0142). The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.