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A New Anti-loxoscelic Serum Produced Against Recombinant Sphingomyelinase D: Results of Preclinical Trials

Envenomation by Loxosceles species (brown spider) can lead to local dermonecrosis and to serious systemic effects. The main toxic component in the venom of these spiders is sphingomyelinase D (SMase D) and various isoforms of this toxin are present in Loxosceles venoms. We have produced a new anti-loxoscelic serum by immunizing horses with recombinant SMase D. In the present study, we compared the neutralization efficacy of the new anti-loxoscelic serum and anti-arachnidic serum (the latter serum is used for therapy for loxoscelism in Brazil) against the toxic effects of venoms from spiders of the genus Loxosceles. Neutralization tests showed that anti-SMase D serum has a higher activity against toxic effects of L. intermedia and L. laeta venoms and similar or slightly weaker activity against toxic effects of L. gaucho than that of Arachnidic serum. These results demonstrate that recombinant SMase D can replace venom for anti-venom production and therapy.

Received June 3, 2008. Accepted for publication June 11, 2008.

Financial support: This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, and the Butantan Foundation.

^* Address correspondence to Denise V. Tambourgi, Laboratório de Imunoquímica, Instituto Butantan, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, São Paulo, Brazil. E-mail: dvtambourgi{at}butantan.gov.br

Authors’ addresses: Daniel Manzoni de Almeida, Rute M. Gonçalves de Andrade, and Denise V. Tambourgi, Laboratório de Imunoquímica, Instituto Butantan, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, São Paulo, Brazil, E-mails: daniel{at}butantan.gov.br, rutemgdeandrade{at}butantan.gov.br, and dvtambourgi{at}butantan.gov.br. Matheus de F. Fernandes-Pedrosa, Laboratório de Imunoquímica, Instituto Butantan, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, São Paulo, Brazil and Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil, E-mail: mpedrosa{at}ufrnet.br. José Roberto Marcelino and Hisako Gondo-Higashi, Di-visão Bioindustrial, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, São Paulo, Brazil, E-mails: marcelino{at}butantan.gov.br and hisa{at}butantan.gov.br. Inácio de L. M. Junqueira de Azevedo and Paulo Lee Ho, Centro de Biotecnologia, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, São Paulo, Brazil, E-mails: ijuncaze{at}butantan.gov.br and hoplee{at}butantan.gov.br. Carmen van den Berg, Cardiff University, Wales College of Medicine, Cardiff CF10 3XQ, United Kingdom, E-mail: vandenbergcw{at}yahoo.com.