*4.7. Statistical Analysis*

Statistical analysis was performed by GraphPad Prism software. ANOVA (Tukey's multiple comparison test) was used to compare average antibody titer obtained between antisera of animal groups, orally tolerized or not with *B. jararaca* venom. The sera obtained at different times after immunization were submitted to analyses. Two-way ANOVA with 95% confidence intervals was used to determine significant differences between IgG1 and IgG2a antibody titers for each mouse group.

**Author Contributions:** Conceptualization, O.A.S.; methodology, L.R.T. and O.A.S.; validation, L.R.T. and O.A.S.; formal analysis, L.R.T., D.V.T. and O.A.S.; investigation, L.R.T. and O.A.S.; resources, A.M.M., D.V.T. and O.A.S.; data curation, L.R.T.; writing—original draft preparation, L.R.T.; writing review and editing, L.R.T., A.M.M. and D.V.T.; visualization, L.R.T., A.M.M., D.V.T. and O.A.S.; supervision, O.A.S.; project administration, O.A.S.; funding acquisition, A.M.M., D.V.T. and O.A.S. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Brazilian National Council for Scientific and Technological Development (CNPq), grant number 474435/2007-5, by INCTTOX (Instituto Nacional de Ciência e Tecnologia em Toxinas) from the São Paulo Research Foundation (FAPESP) and CNPq, and by FAPESP (grant number 2017/17844-8). A.M.M. is grateful for CNPq (process 307405/2020-0).

**Institutional Review Board Statement:** The methodology of this work was approved by Ethic Committee on Animal Use of the Butantan Institute (Protocol IBU 454/08, 9 April 2008).

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data presented in this study are available on request from corresponding author.

**Acknowledgments:** We thank Stephanie Murari do Nascimento for technical support.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

