Inter-individual variability in equine antibody responses to African snake venoms follows heavy-tailed distributions with implications for antivenom production

Posted by
  Inter-individual variability in equine antibody responses to African snake venoms follows heavy-tailed distributions with implications for antivenom production Abstract Variability in the antibody response of horses used for snake antivenom manufacture is well recognized, yet its statistical structure and implications for industrial productivity remain poorly characterized. In this study, we quantified antivenom antibody titers by ELISA in a cohort of 14 horses immunized with venoms from the clinically most important snakes in sub-Saharan Africa. To integrate antibody levels with plasma availability, we calculated the Cumulative Plasma Productivity (CPP) by converting individual plasma volumes into titer-corrected equivalents and sequentially pooling these volumes according to their corrected contribution. Distributional analysis revealed right-skewed, heavy-tailed patterns better approximated by a log-normal model than by a strict Pareto (power-law) form, with approximately 20–3...

Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. variegata

Posted by

 


Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. variegata

Abstract

Brown spider envenomation (loxoscelism) represents a significant public health concern in South America, yet most studies focus on a few medically recognized species. Here, we provide the first molecular and functional characterization of the venom gland extract from Loxosceles aff. variegata (LafvVGE), a brown spider collected in synanthropic habitats in Ituiutaba, Minas Gerais, Brazil. SDS-PAGE and immunoblot analyses revealed prominent protein bands consistent with phospholipase D (PLD) toxins, the main agents of loxoscelism symptoms. ELISA assays demonstrated that LafvVGE is effectively recognized by Brazilian therapeutic antivenoms, indicating immunological cross-reactivity. Enzymatic assays confirmed sphingomyelinase and collagenase/gelatinase activities comparable to those of Loxosceles gaucho (a species of acknowledged medical relevance), although LafvVGE from female individuals showed higher activities than male derived pools under our experimental conditions. Neutralization assays showed complete inhibition of sphingomyelinase activity but only partial inhibition of gelatinase activity by the anti-loxoscelic antivenom, highlighting differential susceptibility of venom components to antivenom-mediated neutralization under in vitro conditions. Molecular analysis of venom gland transcripts identified eight distinct PLD isoforms (LafvPLD1–8), all containing conserved catalytic and metal-binding residues characteristic of class II Loxosceles PLDs. Structural modeling revealed isoform-specific variations in the aromatic cage motif and electrostatic surface, suggesting potential effects on membrane interactions and substrate specificity. Collectively, these findings place L. aff. variegata within the biochemical and structural spectrum of medically relevant Loxosceles species, expanding comparative knowledge of PLD diversity and function. While clinical relevance remains to be established in vivo, this study underscores the value of integrating biochemical, immunological, and structural analyses to identify emerging venom phenotypes with potential implications for surveillance and antivenom coverage.
Silva-Araújo, A. L., Silva-Magalhães, R., Peres-Damásio, P., Pereira, E. H. T., De Oliveira Souza, R., Varela, L. S. D. R. N., Ribeiro Tomé, L. M., Campos de Melo Iani, F., Silveira, A. L., Borges, M. H., Medina-Santos, R., Chavez-Olórtegui, C., Vasconcelos Diniz, M. R., Bittencourt Paiva, A. L., & Guerra-Duarte, C. (2026). Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. Variegata. Toxicon, 109129. https://doi.org/10.1016/j.toxicon.2026.109129