Snake envenomation is a seriousmedical problem and antivenoms are the main treatment. Antisera are produced byimmunization of horses with snake venom using complete Freund?s adjuvant andincomplete (booster) but it causes severe local reactions. A new adjuvantstrategy is here proposed to increase efficiency in antisera production undermuch less morbilty to immunized animals. Previous works showed that CpG-ODNformulated with a 6-O-ascorbyl palmitate nanostructure (Coa-ASC16) was moreefficient as adjuvant than CpG-ODN alone using ovalbumin (OVA) as an antigenmodel. Here, we evaluated the immune response induced by this adjuvant strategyusing crotalic PLA₂ enzymeas antigen. Balb/c mice were subcutaneously immunizated on days 0, 15 and 30with PLA₂/CpG-ODN/Coa-ASC16or PLA₂/Freund?s Adyuvant (complete first and incomplete-booster)(dose/mice: crotalic PLA₂: 10-15μg, CpG-ODN: 30 μg). On day 50, mice weresacrificed. In both immunized group mice, the antibody titers in plasma were high(dilution1/24800), with a similar IgG1/IgG2a ratio. The IgG antibodies werethen purified by affinity Sepharose-proteinG column. Indirect hemolyticactivity neutralization of the PLA₂(2.5 μg) with specific antibodies(1.7-4.5 μg range; IgG anti-PLA₂) were made by radial hemolisis. Theevaluation did not show difference neutralizing capacity ofthe antibodies produced by CpG-ODN/Coa-ASC16 or Freund?s Adyuvant. Macroscopic andmicroscopic analysis at the site of injection of mice inoculated with Freund?sadjuvant showed local damage (with non-infectious abscesses) and hypertrophy ofinguinal lymph nodes, whereas mice injected with CpG-ODN/Coa-ASC16 did not. Our results showthat CpG-ODN/Coa-ASC16 produces ahumoral response as strong and specific as Freund´sadjuvant, with minor or nulllocal deleterious effect, So, this complex emerge as a new adjuvant, a veryattractive alternative for  anticrotalic sera production.