Orally Administrated Recombinant Vaccinia Virus Displaying ROP4 Induces Protection against Toxoplasma gondii Challenge Infection

Abstract

Recombinant vaccinia viruses (rVVs) are attenuated viruses and are widely utilized as vectored vaccine platforms against numerous diseases. However, the protective efficacy of these rVV vaccines against Toxoplasma gondii and the resulting mucosal immunity has not been thoroughly assessed. Here, rVVs expressing the rhoptry protein 4 (ROP4) of T. gondii were generated. To evaluate the protection induced by the vaccines, mice were orally immunized with the ROP4-rVVs and subsequently challenge-infected with a lethal dose of T. gondii ME49 strain. Immunization with the rVVs induced higher levels of parasite-specific IgG and IgA antibody responses in sera compared to unimmunized control (NC). Upon challenge infection, significantly higher levels of IgG or IgA antibody responses in the brain, intestines, and vaginal samples were found in the immunized mice compared to NC. The ROP4-rVV vaccination elicited potent IgG and IgA secreting cell (ASC) responses, while substantially enhancing germinal center B cell, as well as CD4+ and CD8+ T cell responses from lymphoid organs. The production of pro-inflammatory cytokines IFN-γ and IL-6 in the brains was markedly diminished following immunization. The immunized mice also experienced reduced bodyweight loss and possessed fewer brain cysts than the control group. These results suggest that oral delivery of ROP4 displaying rVVs induced mucosal and systemic immunities that contributed to protection against lethal T. gondii challenge infection.

Toxoplasma rhoptry proteins that affect encephalitis outcome

“…The roles of ROP4 include the regulation of host cell invasion, parasitic proliferation, and parasitic virulence regulation [ 24 ]. At present, research on ROP4 has mainly focused on various vaccines, including oral recombinant vaccines [ 25 ], virus-like particle (VLP) vaccines [ 26 ], recombinant baculovirus vaccines [ 27 ], and others. Research has shown that compared to a combination of two vaccines (ROP4VLP + ROP13VLP), the single ROP (4 + 13) VLP vaccine better promoted the expression of IgG, IgG1, IgG2a, and IgA in mouse serum.…”

“… ROP39 ROP39 mediates an IRGB10-specific parasitic effect and regulates acute Toxoplasma virulence [ 24 ]. ROP54 ROP54 has been recommended as a vaccine candidate for toxoplasmosis [ 25 ]. ROP54 modulates T. gondii virulence and host GBP2 loading [ 26 ].…”

Mineralization Reduces the Toxicity and Improves Stability and Protective Immune Response Induced by Toxoplasma gondii

“…Vaccination is one of the most significant achievements for controlling and preventing infectious diseases; it is also an ideal strategy for toxoplasmosis [ 6 , 7 ]. Current studies on the T. gondii vaccine mainly focused on killed vaccines, live attenuated vaccines [ 8 ], specific component vaccines [ 9 , 10 ], subunit vaccines [ 11 ] and nucleic acid vaccines [ 12 ]. Immunoprotection is still an important challenge for the T. gondii vaccine.…”