Engineered antigen containing epitopes from Loxosceles spp. spider toxins induces a monoclonal antibody (Lox-mAb3) against astacin-like metalloproteases

Costa, Tamara G.F.; Costal-Oliveira, Fernanda; Assis, Thamyres C.S. de; Lima, Sabrina A.; Martins, Christina A.; Finco, Alessandra Becker; Veiga, Sílvio Sanches; Soccol, Vanete Thomaz; Machado-de-Ávila, Ricardo Andrez; Figueiredo, Luís Gustavo Girardi; Minozzo, João Carlos; Kalapothakis, Evanguedes; Guerra-Duarte, Clara; Alvarenga, Larissa M.; Chávez-Olortégui, Carlos

doi:10.1016/j.ijbiomac.2020.06.176

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…These data were later confirmed by molecular cloning of members of metalloprotease family, strengthening the existence of various isoforms of these proteases in the brown spider venoms [ 46 ]. The existence of families of astacins in the venoms of brown spiders was also demonstrated by the use of a monoclonal antibody produced against a L. intermedia LALP isoform, which cross-reacted with crude venoms of L. laeta and L. gaucho and neutralized the proteolytic effects of these enzymes in the venoms [ 47 ]. The biological conservation and the presence of astacin isoforms in different brown spider venoms have already pointed out the participation of these proteolytic enzymes in the biological events related to brown spider venom.…”

Section: Methodsmentioning

confidence: 99%

Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins?

Gremski

Matsubara

Justa

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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Accidents caused by the bites of brown spiders (Loxosceles) generate a clinical condition that often includes a threatening necrotic skin lesion near the bite site along with a remarkable inflammatory response. Systemic disorders such as hemolysis, thrombocytopenia, and acute renal failure may occur, but are much less frequent than the local damage. It is already known that phospholipases D, highly expressed toxins in Loxosceles venom, can induce most of these injuries. However, this spider venom has a great range of toxins that probably act synergistically to enhance toxicity. The other protein classes remain poorly explored due to the difficulty in obtaining sufficient amounts of them for a thorough investigation. They include astacins (metalloproteases), serine proteases, knottins, translationally controlled tumor proteins (TCTP), hyaluronidases, allergens and serpins. It has already been shown that some of them, according to their characteristics, may participate to some extent in the development of loxoscelism. In addition, all of these toxins present potential application in several areas. The present review article summarizes information regarding some functional aspects of the protein classes listed above, discusses the directions that could be taken to materialize a comprehensive investigation on each of these toxins as well as highlights the importance of exploring the full venom repertoire.

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Section: Methodsmentioning

confidence: 99%

Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins?

Gremski

Matsubara

Justa

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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“…The chimeric protein rMEPlox mentioned earlier was also used as antigen to produce a monoclonal antibody named Lox-mAb3. This mAb recognized a metalloprotease of L. intermedia, crossreacted with metalloproteases of L. laeta and L. gaucho, and neutralized the fibrinogenolytic activity of L. intermedia venom, which may decrease hemorrhagic disturbances caused by Loxosceles envenomation (Costa et al, 2020).…”

Section: Systemic Injury (Main) and Cutaneous Lesionmentioning

confidence: 99%

“…Development of a second generation antivenom produced from mutant PLDs or engineered peptides/chimeric proteins based on PLDs(Mendes et al (2013),Vuitika et al (2016),Lima et al (2018),Calabria et al (2019), daSilva et al (2021)) 2. Development of monoclonal antibodies that cross-react with venom PLDs(Alvarenga et al (2003,Karim-Silva et al (2016),Costa et al (2020)) 3. Development of a vaccine for areas where the accidents are endemic(Lima et al (2018), daSilva et al (2021))• Biotool to be used in studies regarding tumor cell biology(Wille et al (2013), Siqueira et al (2019)) • Antimicrobial drug (Segura-Ramírez and Silva Júnior.…”

mentioning

confidence: 99%

Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs

Gremski

Matsubara

Polli

et al. 2021

Front. Mol. Biosci.

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Brown spider (genus Loxosceles) venoms are mainly composed of protein toxins used for predation and defense. Bites of these spiders most commonly produce a local dermonecrotic lesion with gravitational spread, edema and hemorrhage, which together are defined as cutaneous loxoscelism. Systemic loxoscelism, such as hematological abnormalities and renal injury, are less frequent but more lethal. Some Loxosceles venom toxins have already been isolated and extensively studied, such as phospholipases D (PLDs), which have been recombinantly expressed and were proven to reproduce toxic activities associated to the whole venom. PLDs have a notable potential to be engineered and converted in non-toxic antigens to produce a new generation of antivenoms or vaccines. PLDs also can serve as tools to discover inhibitors to be used as therapeutic agents. Other Loxosceles toxins have been identified and functionally characterized, such as hyaluronidases, allergen factor, serpin, TCTP and knottins (ICK peptides). All these toxins were produced as recombinant molecules and are biologically active molecules that can be used as tools for the potential development of chemical candidates to tackle many medical and biological threats, acting, for instance, as antitumoral, insecticides, analgesic, antigens for allergy tests and biochemical reagents for cell studies. In addition, these recombinant toxins may be useful to develop a rational therapy for loxoscelism. This review summarizes the main candidates for the development of drugs and biotechnological inputs that have been described in Brown spider venoms.

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“…Loxoscelic envenoming treatment is based on observed clinical signs and includes the use of dapsone, acetylsalicylic acid, broad spectrum antibiotics, corticosteroids, specific antivenom, composed of heterologous antibodies developed in horses and new antibody treatments (5,9,10,11,12,13) . Despite these treatment options, tissue recovery after extensive dermonecrotic damage is slow and scar formation is difficult.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of mesenchymal cells and dapsone for the treatment of dermonecrotic wounds caused by Loxosceles laeta venom in rabbits

et al. 2022

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This study aimed to evaluate the efficacy of mesenchymal stem cells (MSC), alone or associated with dapsone (DAP), in treating dermonecrotic wounds caused by Loxosceles laeta venom. Twenty-five male rabbits were distributed into five groups. Negative control received ultrapure water (C-), whilst all other groups were injected with 20 μg of L. laeta venom. After 4 hours, each group received one of the following treatments: PBS (C+), DAP, MSC, and DAP+MSC. Animals were evaluated daily and photographic records made for analysis of wound area. Twelve days after, animals were euthanized and skin samples removed for histological analysis. We observed that DAP showed the best percentage of wound contraction at day 3. In the treatments using MSCs, a negative value of wound contraction was observed for the isolated MSCs, as well as a lower contraction value for the association of the MSC + DAP when compared to PBS, probably, by the increase in initial infammation after the application of stem cells, due to the fact that MSCs secrete a broad spectrum of bioactive molecules such as cytokines and growth factors that favor regeneration. Histologically, it was observed that animals of C+ showed extensive areas of necrosis, ulcers, neutrophilic infiltrate, and mineralization. Collagen deposition showed increase in MSC+DAP treatment, however vascularization remained unchanged. This is the first report using MSC and MSC+DAP as a treatment for cutaneous loxoscelism and more studies are needed to determine its use as an alternative therapy for dermonecrotic lesions caused by Loxosceles spider.

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Engineered antigen containing epitopes from Loxosceles spp. spider toxins induces a monoclonal antibody (Lox-mAb3) against astacin-like metalloproteases

Cited by 8 publications

References 35 publications

Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins?

Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins?

Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs

Evaluation of mesenchymal cells and dapsone for the treatment of dermonecrotic wounds caused by Loxosceles laeta venom in rabbits

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