Protective humoral immunity induced by virus-like particles expressing Toxoplasma gondii CST1 or MIC8

Protective efficacy assessment of toxoplasmosis vaccines, at least at the preclinical level, frequently involves lethal dose challenge infection. Nonetheless, their efficacies remain largely unexplored against low infection doses which better reflects how humans become infected in the real world. In this study, we compared the immunity elicited in mice that were heterologously immunized with recombinant baculovirus and virus-like particles expressing either the cyst wall protein (CST1) or microneme protein 8 (MIC8) of Toxoplasma gondii (T. gondii). We also investigated how these vaccines fared against both light and heavy infection intensities of T. gondii ME49. Interestingly, under light infection intensity, vaccines expressing CST1 induced significantly higher mucosal antibody responses than MIC8. Germinal center B (GC B) cell responses were elicited to a greater extent following immunization with either antigen, regardless of the infection dose. Similarly, both antigens suppressed IFN-γ production in the brains upon heavy infection. The overall vaccine-induced protection was also similar for the two vaccine antigens under heavy infection. However, in lightly infected mice, CST1 conferred improved GC B cell induction and further inhibited IFN-γ and cyst burden than those elicited by MIC8, thereby contributing to better protection. These findings indicated that light infection could be used to identify optimal vaccine candidates, thus highlighting the impact of infection intensity in vaccine efficacy evaluations.