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

VANESA R. SÁNCHEZ, IGNACIO M. FENOY, MARIANO S. PICCHIO, ARIADNA S. SOTO, NADIA ARCON, ALEJANDRA GOLDMAN, VALENTINA MARTIN

ACTA TROPICA

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015

0001-706X

Subunit-based vaccines are safer than live orattenuated pathogen vaccines, although they are generally weak immunogens.Thus, proper combination of immunization strategies and adjuvants are needed toincrease their efficacy. We have previously protected C3H/HeN mice from Toxoplasmagondii infection by immunization with the serine protease inhibitor-1(TgPI-1) in combination with alum. In this work, we explore an originalvaccination protocol that combines administration of recombinant TgPI-1 byintradermal and intranasal routes in order to enhance protection in the highlysusceptible C57BL/6 strain. Mice primed intradermally with rTgPI-1 plus alumand boosted intranasally with rTgPI-1 plus CpG-ODN elicited a strong specificTh1/Th2 humoral response, along with a mucosal immune 30 response characterizedby specific-IgA in intestinal lavages. A positive cellular response of mesenthericlymph node cells and Th1/Th2 cytokine secretion in the ileon were also 32 detected.When immunized mice were challenged with the cystogenic Me49 T. gondii  strain, they displayed up to 62 % reduction inbrain parasite burden. Moreover, adoptive transfer of mesenteric lymph nodecells from vaccinated to naïve mice induced significant protection againstinfection. These results demonstrate that this strategy that combines the  administration of TgPI-1 by two differentroutes, intradermal priming and intranasal boost,  improves protective immunity against T.gondii chronic infection in highly susceptible mice