Camelid-derived antibodies reduce myonecrosis and IL-1β release after treatment with Bothrops jararacussu venom in mice

Snakebite envenoming in Latin America is both an occupational hazard and a neglected tropical disease. Globally, more than 420,000 envenomings occur annually, resulting in approximately 20,000 deaths. In Brazil, most cases are caused by snakes of the genus Bothrops, which comprises over 60 species distributed throughout the country. Although antivenom therapy efficiently neutralizes systemic effects, local manifestations such as myonecrosis, dermonecrosis, pain, and edema remain poorly controlled. These effects are largely mediated by snake venom phospholipases A₂ (svPLA₂s), which play a central role in cytotoxicity, myotoxicity, and local inflammation. Camelid hyperimmune serum contains heavy-chain antibodies (HcAbs; IgG2 and IgG3) that lack light chains and display reduced immunogenicity and enhanced tissue penetration, making them promising candidates as adjunct antivenom therapies. This study aimed to investigate the ability of Lama glama HcAbs (LHcAbs) to modulate local inflammatory responses and their association with NLRP3 inflammasome activation in experimental envenomation. LHcAbs were purified from hyperimmune serum obtained after immunization with whole venom and PLA₂ from Bothrops jararacussu venom (BjV) using Protein A and G Sepharose columns. Swiss mice received intramuscular injections of BjV into the gastrocnemius muscle, followed by LHcAbs treatment. Plasma analyses showed significant reductions in biomarkers of muscle damage (creatine kinase and lactate dehydrogenase) and cardiac injury (CK-MB) in treated animals. Aspartate aminotransferase levels were reduced, whereas alanine aminotransferase levels remained unchanged. Notably, LHcAbs treatment significantly decreased IL-1β levels in muscle tissue and attenuated NLRP3 inflammasome activation. These findings demonstrate that LHcAbs effectively reduce local tissue damage and inflammation, supporting their potential as complementary therapeutics to conventional antivenom therapy. • Llama heavy-chain antibodies (LHcAbs) showed high reactivity against B. jararacussu venom and its phospholipases. • LHcAbs showed strong reactivity against various Bothrops toxins and venoms and recognized Crotalus venoms and toxins. • LHcAbs reduced myotoxicity, cytotoxicity, and TGO levels in mice, demonstrating systemic protective action. • LHcAbs treatment decreased IL-1β and NLRP3, indicating anti-inflammatory effect. • LHcAbs demonstrated potential as an adjuvant therapy to conventional Antivenom.