Assessing SABU (Serum Anti Bisa Ular), the sole Indonesian antivenom: A proteomic analysis and neutralization efficacy study

Abstract

Serum Anti Ular Bisa (SABU) is the only snake antivenom produced locally in Indonesia; however, its effectiveness has not been rigorously evaluated. This study aimed to assess the protein composition and neutralization efficacy of SABU. SDS polyacrylamide gel electrophoresis, size-exclusion liquid chromatography and shotgun proteomics revealed that SABU consists of F(ab’)2 but a significant amount of dimers, protein aggregates and contaminant albumins. SABU moderately neutralized Calloselasma rhodostoma venom (potency of 12.7 mg venom neutralized per ml antivenom, or 121.8 mg venom per g antivenom protein) and Bungarus fasciatus venom (0.9 mg/ml; 8.5 mg/g) but it was weak against the venoms of Naja sputatrix (0.3 mg/ml; 2.9 mg/g), Naja sumatrana (0.2 mg/ml; 1.8 mg/g) and Bungarus candidus (0.1 mg/ml; 1.0 mg/g). In comparison, NPAV, the Thai Neuro Polyvalent Antivenom, outperformed SABU with greater potencies against the venoms of N. sputatrix (0.6 mg/ml; 8.3 mg/g), N. sumatrana (0.5 mg/ml; 7.1 mg/g) and B. candidus (1.7 mg/ml; 23.2 mg/g). The inferior efficacy of SABU implies that a large antivenom dose is required clinically for effective treatment. Besides, the antivenom contains numerous impurities e.g., albumins that greatly increase the risk of hypersensitivity. Together, the findings indicate that the production of SABU warrants further improvement.

Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise

“…Despite a number of recent reports suggesting that certain antivenoms might have greater paraspecificity than previously anticipated (e.g. Pla et al , ; Tan et al , ), there are also a number of reports describing the poor performance or failure of antivenoms at neutralising venom from snakes related to those used for immunisation (Casewell et al , ; Segura et al , ; Tan et al , ). Limitations with the paraspecificity of antivenoms are best exemplified by reports from sub‐Saharan Africa where geographically inappropriate products were used to treat snakebite in the Central African Republic and Ghana, resulting in increases in case fatality rates from 0·4% and 1·0% to 10·0% and 12·1% respectively (Visser et al , ; Alirol et al , ).…”

“…The antibodies present in any antivenom are specific to those venoms that were used for immunisation. Whilst these antibodies might cross‐react with and neutralise similar venom toxins present in different species than those used for immunisation, there will be a limit to their cross‐efficacy, and this is often restricted to the same genus of snakes (Williams et al , ; Tan et al , ,b). Despite a number of recent reports suggesting that certain antivenoms might have greater paraspecificity than previously anticipated (e.g.…”

Venom proteomics and antivenom neutralization for the Chinese eastern Russell’s viper, Daboia siamensis from Guangxi and Taiwan

“…Immunological binding activity was expressed as percentage of relative absorbance (highest binding activity set as 100%) between two comparing antivenoms in immunological binding toward the both D . siamensis venoms (Ds-Guangxi and Ds-Taiwan) 96 . Values were means of triplicates ± S.E.M., and the significance of difference was analyzed using unpaired t-test with p value <0.05.…”

“…Procoagulant effect of the venom was determined by adding 100 µl of citrated human plasma (containing 40 µl of 0.4 M CaCl 2 /ml) to 100 µl of D . siamensis venoms of various concentrations in saline at 37 °C according to a modified turbidimetric method 96 , 97 . The absorbance at 405 nm was monitored every 30 s over 30 min.…”

Proteomics and antivenom immunoprofiling of Russell’s viper (Daboia siamensis) venoms from Thailand and Indonesia

“…Unfortunately, in Indonesia, there is no locally produced antivenom against the Indonesian D. siamensis. This has led to the use of inappropriate, non-specific Indonesian antivenom, Serum Anti Bisa Ular (SABU, indicated for treatment of envenoming by the Javan spitting cobra, banded krait and Malayan pit viper) [20,21]. A recent study demonstrated that the procoagulant and lethal effects of D. siamensis from Indonesia (Ds-Indonesia) venom can be effectively neutralized by DsMAV-Thailand but, importantly, not SABU [22].…”