Homologous prime-boost strategy with TgPI-1 improves the immune response and protects highly susceptible mice against chronic Toxoplasma gondii infection

• Published in: Acta tropica 2015-10, Vol.150, p.159-165
• Main Authors: Sánchez, Vanesa R., Fenoy, Ignacio M., Picchio, Mariano S., Soto, Ariadna S., Arcon, Nadia, Goldman, Alejandra, Martin, Valentina
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; Alum Compounds - administration & dosage; Animals; Drug Administration Schedule; Female; Immunity, Mucosal; Injections, Subcutaneous; Mice; Mice, Inbred C57BL; Mucosal immunity; Prime-boost strategy; Protozoan Proteins - administration & dosage; Protozoan Vaccines - immunology; Serin protease inhibitor-1; Subunit vaccine; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis, Animal - immunology; Toxoplasmosis, Animal - prevention & control; Vaccination
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2015.07.013

rTgPI-1 prime-boost strategy protects highly susceptible C57BL/6 mice against chronic T. gondii infection by the induction of systemic and mucosal immune responses. [Display omitted] •TgPI-1 prime-boost strategy improves immunity in C57BL/6 mice against toxoplasmosis.•Different vaccination strategies for the delivery of a particular antigen.•Combination of two routes of immunization improves protection against Toxoplasmosis.•Immuno-protection correlates with induction of mucosal and systemic immune responses.•Vaccine formulation including safe and effective adjuvants suitable to use in humans. Subunit-based vaccines are safer than live or attenuated pathogen vaccines, although they are generally weak immunogens. Thus, proper combination of immunization strategies and adjuvants are needed to increase their efficacy. We have previously protected C3H/HeN mice from Toxoplasma gondii infection by immunization with the serine protease inhibitor-1 (TgPI-1) in combination with alum. In this work, we explore an original vaccination protocol that combines administration of recombinant TgPI-1 by intradermal and intranasal routes in order to enhance protection in the highly susceptible C57BL/6 strain. Mice primed intradermally with rTgPI-1 plus alum and boosted intranasally with rTgPI-1 plus CpG-ODN elicited a strong specific Th1/Th2 humoral response, along with a mucosal immune response characterized by specific-IgA in intestinal lavages. A positive cellular response of mesentheric lymph node cells and Th1/Th2 cytokine secretion in the ileon were also detected. When immunized mice were challenged with the cystogenic Me49 T. gondii strain, they displayed up to 62% reduction in brain parasite burden. Moreover, adoptive transfer of mesenteric lymph node cells from vaccinated to naïve mice induced significant protection against infection. These results demonstrate that this strategy that combines the administration of TgPI-1 by two different routes, intradermal priming and intranasal boost, improves protective immunity against T. gondii chronic infection in highly susceptible mice.