Protective immunity induced by CpG ODN‐adjuvanted virus‐like particles containing Toxoplasma gondii proteins

Abstract

Aims To date, a Toxoplasma gondii vaccine for clinical use remains unavailable, though multiple vaccine candidates have been suggested. In our previous studies, unadjuvanted virus‐like particles (VLPs) vaccines expressing multiple T. gondii antigens were confirmed to be protective against T. gondii challenge infection. Yet, the protective efficacy of adjuvanted T. gondii VLP in comparison with the unadjuvanted counterpart requires elucidation. Methods and Results In the present study, mice were immunized with the multi‐antigenic VLP vaccines (TG146 VLP) with or without CpG adjuvants and their protective efficacies were compared. CpG‐adjuvanted TG146 VLP vaccine elicited enhanced T gondii‐specific IgG and IgA antibody responses in the sera, mucosal tissue and the brain compared to unadjuvanted VLPs vaccine. Inclusion of CpG adjuvant in vaccines also induced greater CD4+ and CD8+ T‐cell responses, as well as B cell and germinal centre B cell responses from splenocytes and mesenteric lymph nodes. Pro‐inflammatory cytokine response and cyst counts in the brain were drastically diminished in mice immunized with CpG‐adjuvanted VLP vaccines. Conclusion Our results demonstrated that CpG‐adjuvanted T. gondii VLPs can significantly enhance the protective efficacy of vaccines against T. gondii infection.

Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

“…Notably, while the ROP4-rBVs used in the present study only elicited strong antibody responses in the intestines, ROP4 VLPs from our previous work induced the production of vast quantities of vaginal, urinal, fecal, and intestinal IgG. In many of our previous studies investigating the protective efficacy of T. gondii VLP vaccines, unimmunized mice perished around 30 dpi when infected with 450 cysts ( Kang et al., 2019 ; Kang et al., 2020a ; Kang et al., 2021a ; Kang et al., 2021b ). In the present study, unimmunized mice died by 16 dpi which was attributed to the high infection dose exceeding 450 cysts.…”

Passive Immunity and Antibody Response Induced by Toxoplasma gondii VLP Immunization

“…At 30 days post-infection (dpi), the mouse brain tissues were isolated for cyst counting, as previously described [ 22 ]. Mice that lost 20% of initial bodyweight were humanely euthanized, as described [ 21 , 23 ].…”

“…The immunized mice were challenge-infected orally with a lethal dose of 450 ME49 cysts 30 days after immunization. Mice that lost 20% of their initial bodyweight were considered dead and were humanely euthanized as described [ 21 , 23 ].…”

“…To date, VLP vaccine efficacies against T. gondii infections were mostly evaluated following a prime-boost immunization regimen [ 19 , 20 , 21 ]. Recently, in our previous study, the protective efficacies of CpG-ODN adjuvanted T. gondii VLPs from mice receiving a differing number of immunizations were assessed [ 22 , 23 ]. Although limited information has been presented for a single immunization, the results of our previous study revealed that VLP-immunization induces potent levels of parasite-specific antibody responses, which signified its potential application in passive immunization studies.…”

Advances in Toxoplasma gondii Vaccines: Current Strategies and Challenges for Vaccine Development

“…Supplementing VLP vaccines with adjuvants, as with other vaccine platforms, strengthened the protective efficacy of the vaccines. Multi-antigenic VLPs adjuvanted with the Toll-like receptor 9 agonist CpG ODN enhanced both humoral and cellular immune responses in mice and further limited cyst formation in comparison to unadjuvanted VLPs [ 85 ]. Using the identical VLP vaccine, increasing the number of immunizations was also effective at reducing the cyst counts [ 86 ].…”