Expanding anti-venom strategies: Camelid polyclonal antibodies with high capacity to recognize snake venom.

Autor:	Campos Farias BJ; Laboratório de Engenharia de Anticorpos, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil; Programa de Pós-graduação em Biologia Experimental, PGBIOEXP, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil., Makoto Kayano A; Laboratório de Biotecnologia de Proteínas e Compostos Bioativos Aplicados à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil., Barros Luiz M; Instituto Federal de Educação, Ciência e Tecnologia de Rondônia, IFRO, Porto Velho-RO, Brazil., Maciel DE Lima A; Laboratório de Biotecnologia de Proteínas e Compostos Bioativos Aplicados à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil., Suelen da Silva Morais M; Laboratório de Engenharia de Anticorpos, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil., Moreira Mendes L; Laboratório de Engenharia de Anticorpos, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil., Mota Santana H; Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil; Programa de Pós-graduação em Biologia Experimental, PGBIOEXP, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil., Reis Prado ND; Laboratório de Engenharia de Anticorpos, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil., Andrade Roberto S; Laboratório de Engenharia de Anticorpos, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil; Programa de Pós-graduação em Biologia Experimental, PGBIOEXP, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil., Martins Soares A; Laboratório de Biotecnologia de Proteínas e Compostos Bioativos Aplicados à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil., Pavan Zuliani J; Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil; Programa de Pós-graduação em Biologia Experimental, PGBIOEXP, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil., Pereira SDS; Laboratório de Engenharia de Anticorpos, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho-RO, Brazil; Programa de Pós-graduação em Biologia Experimental, PGBIOEXP, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil., Celedonio Fernandes CF; Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Ceará, Eusébio-CE, Brazil; Programa de Pós-graduação em Biologia Experimental, PGBIOEXP, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil. Electronic address: carla.celedonio@fiocruz.br.
Jazyk:	angličtina
Zdroj:	Toxicon : official journal of the International Society on Toxinology [Toxicon] 2024 Aug 28; Vol. 247, pp. 107837. Date of Electronic Publication: 2024 Jun 28.
DOI:	10.1016/j.toxicon.2024.107837
Abstrakt:	Camelid immunoglobulins represent a unique facet of antibody biology, challenging conventional understandings of antibody diversification. IgG2 and IgG3 in particular are composed solely of heavy chains and exhibit a reduced molecular weight (90 kDa); their elongated complementarity determining region (CDR) loops play a pivotal role in their functioning, delving deep into enzyme active sites with precision. Serum therapy stands as the primary venom-specific treatment for snakebite envenomation, harnessing purified antibodies available in diverse forms such as whole IgG, monovalent fragment antibody (Fab), or divalent fragment antibody F (ab')2. This investigation looks into the intricacies of IgGs derived from camelid serum previously immunized with crotamine and crotoxin, toxins predominantly in Crotalus durissus venom, exploring their recognition capacity, specificity, and cross-reactivity to snake venoms and its toxins. Initially, IgG purification employed affinity chromatography via protein A and G columns to segregate conventional antibodies (IgG1) from heavy chain antibodies (IgG2 and IgG3) of camelid isotypes sourced from Lama glama serum. Subsequent electrophoretic analysis (SDS-PAGE) revealed distinct bands corresponding to molecular weight profiles of IgG's fractions representing isotypes in Lama glama serum. ELISA cross-reactivity assays demonstrated all three IgG isotypes' ability to recognize the tested venoms. Notably, IgG1 exhibited the lowest interactivity in analyses involving bothropic and crotalic venoms. However, IgG2 and IgG3 displayed notable cross-reactivity, particularly with crotalic venoms and toxins, albeit with exceptions such as PLA 2 -CB, showing reduced reactivity, and C. atrox, where IgGs exhibited insignificant reactivity. In Western blot assays, IgG2 and IgG3 exhibited recognition of proteins within molecular weight (≈15 kDa) of C. d. collilineatus to C. d. terrificus, with some interaction observed even with bothropic proteins despite lower reactivity. These findings underscore the potential of camelid heavy-chain antibodies, suggesting Lama glama IgGs as prospective candidates for a novel class of serum therapies. However, further investigations are imperative to ascertain their suitability for serum therapy applications. Competing Interests: Declaration of competing interest The authors 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 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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