Novel insights into the application of recombinant mutated phospholipases D as antigens for developing new strategies against Loxoscelism.

Autor: Polli NLC; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Ferreira MEF; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Schluga PHC; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Antunes BC; Production and Research Center of Immunobiological Products (CPPI), State Department of Health, Piraquara, 83302-200, PR, Brazil., Justa HCD; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Theodoro JL; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Zazula MF; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Naliwaiko K; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Minozzo JC; Production and Research Center of Immunobiological Products (CPPI), State Department of Health, Piraquara, 83302-200, PR, Brazil., Senff-Ribeiro A; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Wille ACM; Department of Structural, Molecular Biology and Genetics, State University of Ponta Grossa (UEPG), Ponta Grossa, 84030-900, PR, Brazil., Veiga SS; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil., Gremski LH; Department of Cell Biology, Federal University of Paraná (UFPR), Curitiba, 81530-900, PR, Brazil. Electronic address: luizagremski@ufpr.br.
Jazyk: angličtina
Zdroj: Acta tropica [Acta Trop] 2024 Oct; Vol. 258, pp. 107354. Date of Electronic Publication: 2024 Aug 04.
DOI: 10.1016/j.actatropica.2024.107354
Abstrakt: Loxoscelism is the pathological condition triggered by a brown spider bite. The venom of these spiders is rich in phospholipases D (PLDs), which can induce virtually all local and systemic manifestations. Recombinant mutated PLDs from clinically relevant Loxosceles species in South America have been investigated as potential antigens to develop novel therapeutic strategies for loxoscelism. However, certain gaps need to be addressed before a clinical approach can be implemented. In this study, we examined the potential of these recombinant mutated PLDs as antigens by testing some variations in the immunization scheme. Furthermore, we evaluated the efficacy of the produced antibodies in neutralizing the nephrotoxicity and sphingomyelinase activity of brown spider venoms. Our findings indicate that the number of immunizations has a greater impact on the effectiveness of neutralization compared to the amount of antigen. Specifically, two or three doses were equally effective in reducing dermonecrosis and edema. Additionally, three immunizations proved to be more effective in neutralizing mice lethality than one or two. Moreover, immunizations mitigated the signs of kidney injury, a crucial aspect given that acute renal failure is a serious systemic complication. In vitro inhibition of the sphingomyelinase activity of Loxosceles venoms, a key factor in vivo toxicity, was nearly complete after incubation with antibodies raised against these antigens. These findings underscore the importance of implementing an effective immunization scheme with multiple immunizations, without the need for high antigen doses, and enhances the spectrum of neutralization exhibited by antibodies generated with these antigens. In summary, these results highlight the strong potential of these antigens for the development of new therapeutic strategies against cutaneous and systemic manifestations of loxoscelism.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Silvio Sanches Veiga reports financial support was provided by National Council for Scientific and Technological Development. Silvio Sanches Veiga reports financial support was provided by Araucaria Foundation. Luiza helena Gremski reports financial support was provided by National Council for Scientific and Technological Development. Nayanne Louise Costacurta Polli reports financial support was provided by National Council for Scientific and Technological Development. Luiza Helena Gremski reports financial support was provided by Federal University of Parana. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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