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

Abstract

Pathogens require physical contact with the mucosal surface of the host organism to initiate infection and as such, vaccines eliciting both mucosal and systemic immune responses would be promising. Studies involving the use of recombinant baculoviruses (rBVs) as mucosal vaccines are severely lacking despite their inherently safe nature, especially against pathogens of global importance such as Toxoplasma gondii. Here, we generated rBVs displaying T. gondii rhoptry protein 4 (ROP4) and evaluated their protective efficacy in BALB/c mice following immunization via intranasal (IN) and oral routes. IN immunization with the ROP4-expressing rBVs elicited higher levels of parasite-specific IgA antibody responses compared to oral immunization. Upon challenge infection with a lethal dose of T. gondii ME49, IN immunization elicited significantly higher parasite-specific antibody responses in the mucosal tissues such as intestines, feces, vaginal samples, and brain than oral immunization. Marked increases in IgG and IgA antibody-secreting cell (ASC) responses were observed from intranasally immunized mice. IN immunization elicited significantly enhanced induction of CD4+, CD8+ T cells, and germinal center B (GC B) cell responses from secondary lymphoid organs while limiting the production of the inflammatory cytokines IFN-γ and IL-6 in the brain, all of which contributed to protecting mice against T. gondii lethal challenge infection. Our findings suggest that IN delivery of ROP4 rBVs induced better mucosal and systemic immunity against the lethal T. gondii challenge infection compared to oral immunization.

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

“…Most of the immunological findings reported here are similar to the protective efficacy induced by ROP4-rBV vaccines as described in our previous study, although several differences in immunological parameters were noted [10]. Consistent with our previous study, a remarkable increase in GC B cells was observed from both the spleens and MLNs of mice.…”

“…Samples were collected as previously described [10]. Four weeks after each immunization, blood samples of mice were collected by retro-orbital plexus puncture.…”

“…T. gondii-specific serum antibody responses were determined as previously described [8,10]. To evaluate ASC induction, splenic and mesenteric lymph nodes (MLNs) were collected from mice.…”

“…Several studies have assessed the efficacy of ROP4 antigens using various vaccine platforms such as virus-like particles (VLPs) [8] or subunit vaccines [9]. Furthermore, we have recently investigated the efficacy of ROP4-expressing recombinant baculovirus (rBV) vaccines and the resulting immune responses in mice [10]. Nevertheless, there are inherent problems with the baculovirus-based vaccines.…”

Protection Induced by Vaccination with Recombinant Baculovirus and Virus-like Particles Expressing Toxoplasma gondii Rhoptry Protein 18

“…Currently, only a few studies investigated the potential of baculovirus-based vaccines against T. gondii [ 9 , 10 ]. Previously, we have also demonstrated that immunizing mice with the recombinant baculovirus (rBV) vaccines expressing the rhoptry protein 4 (ROP4) of T. gondii can induce protection [ 11 ]. Nonetheless, ROP4-rBV immunizations neither completely inhibited cyst formation nor prevented bodyweight loss following T. gondii ME49 challenge infection, which signified the need for further improvements.…”