Prime-boost vaccination with toxoplasma lysate antigen, but not with a mixture of recombinant protein antigens, leads to reduction of brain cyst formation in BALB/c mice

• Published in: PloS one 2015-05, Vol.10 (5), p.e0126334-e0126334
• Main Authors: Wagner, Angelika, Schabussova, Irma, Ruttkowski, Bärbel, Peschke, Roman, Kur, Józef, Kundi, Michael, Joachim, Anja, Wiedermann, Ursula
• Format: Article
• Language: English
• Subjects: ALLERGIC IMMUNE-RESPONSES; Animals; Antibodies; Antibodies, Protozoan - blood; Antibody Specificity - immunology; Antigens; Antigens, Protozoan - immunology; Brain; Brain - parasitology; Brain - pathology; Brain research; Brain tumors; Cells, Cultured; Composition; Cysts; Cytokines; Cytokines - biosynthesis; Developmental stages; DNA - metabolism; Female; Formulations; Gastrointestinal Tract - parasitology; GONDII INFECTION; Helper cells; HOST-CELLS; HUMANS; Immune response; IMMUNIZATION; Immunization, Secondary; Immunocompromised hosts; Immunoglobulin G; Immunology; Incubation; Infections; Interferon; Intestine; Laboratory animals; Lymphocytes T; Macrophages; MAJOR SURFACE PROTEIN; Medical Biotechnology; Medicinsk bioteknologi; Mice; Mice, Inbred BALB C; Nitric oxide; Nitric Oxide - metabolism; Oocysts; PARASITE; Parasite control; Parasites; Parasitology; Patient outcomes; PERORAL INFECTION; Pregnancy; PREVENTION; Priming; Prophylaxis; Proteins; Protozoa; Protozoan Proteins - immunology; Protozoan vaccines; PUBLIC-HEALTH; Recombinant Proteins - immunology; Reduction; Risk factors; Rodents; Spleen - pathology; Splenocytes; Tachyzoites; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis; Trends; Vaccination; Vaccine development; Vaccines; Vero cells; Veterinary medicine; Whooping cough; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126334

Infection with the ubiquitous parasite Toxoplasma gondii is a threat for immunocompromised patients and pregnant women and effective immune-prophylaxis is still lacking. Here we tested a mixture of recombinant T. gondii antigens expressed in different developmental stages, i.e., SAG1, MAG1 and GRA7 (SMG), and a lysate derived from T. gondii tachyzoites (TLA) for prophylactic vaccination against cyst formation. Both vaccine formulations were applied systemically followed by an oral TLA-booster in BALB/c mice. Systemic priming with SMG and oral TLA-booster did not show significant induction of protective immune responses. In contrast, systemic priming and oral booster with TLA induced higher levels of Toxoplasma-specific IgG, IgG1 and IgG2a in sera as well as high levels of Toxoplasma-specific IgG1 in small intestines. Furthermore, high levels of Toxoplasma-specific Th1-, Th17- and Th2-associated cytokines were only detected in restimulated splenocytes of TLA-vaccinated mice. Importantly, in mice orally infected with T. gondii oocysts, only TLA-vaccination and booster reduced brain cysts. Furthermore, sera from these mice reduced tachyzoites invasion of Vero cells in vitro, indicating that antibodies may play a critical role for protection against Toxoplasma infection. Additionally, supernatants from splenocyte cultures of TLA-vaccinated mice containing high levels of IFN-γ lead to substantial production of nitric oxide (NO) after incubation with macrophages in vitro. Since NO is involved in the control of parasite growth, the high levels of IFN-γ induced by vaccination with TLA may contribute to the protection against T. gondii. In conclusion, our data indicate that prime-boost approach with TLA, but not with the mixture of recombinant antigens SMG, induces effective humoral and cellular Toxoplasma-specific responses and leads to significant reduction of cerebral cysts, thereby presenting a viable strategy for further vaccine development against T. gondii infection.