*Article* **Oral Tolerance Induction by** *Bothrops jararaca* **Venom in a Murine Model and Cross-Reactivity with Toxins of Other Snake Venoms**

**Lilian Rumi Tsuruta 1,\*, Ana Maria Moro 1, Denise V. Tambourgi <sup>2</sup> and Osvaldo Augusto Sant'Anna <sup>2</sup>**


**Abstract:** Oral tolerance is defined as a specific suppression of cellular and humoral immune responses to a particular antigen through prior oral administration of an antigen. It has unique immunological importance since it is a natural and continuous event driven by external antigens. It is characterized by low levels of IgG in the serum of animals after immunization with the antigen. There is no report of induction of oral tolerance to *Bothrops jararaca* venom. Here, we induced oral tolerance to *B. jararaca* venom in BALB/c mice and evaluated the specific tolerance and cross-reactivity with the toxins of other *Bothrops* species after immunization with the snake venoms adsorbed to/encapsulated in nanostructured SBA-15 silica. Animals that received a high dose of *B. jararaca* venom (1.8 mg) orally responded by showing antibody titers similar to those of immunized animals. On the other hand, mice tolerized orally with three doses of 1 μg of *B. jararaca* venom showed low antibody titers. In animals that received a low dose of *B. jararaca* venom and were immunized with *B. atrox* or *B. jararacussu* venom, tolerance was null or only partial. Immunoblot analysis against the venom of different *Bothrops* species provided details about the main tolerogenic epitopes and clearly showed a difference compared to antiserum of immunized animals.

**Keywords:** oral tolerance; *Bothrops jararaca*; snake venom; ELISA

**Key Contribution:** We describe the induction of oral tolerance by administration of *Bothrops jararaca* venom through an original approach, showing the main tolerogenic epitopes in *B. jararaca* venom and other species of *Bothrops*.
