Lachesis stenophrys venom reduces the equine antibody response towards Bothrops asper venom used as co-immunogen in the production of polyspecific snake antivenom

Arroyo, Cynthia; Solano, Sergio; Herrera, María; Segura, Álvaro; Estrada, Ricardo; Vargas, Mariángela; Villalta, Mauren; Gutiérrez, José Marı́a; León, Guillermo

doi:10.1016/j.toxicon.2015.06.016

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…Though relatively small in quantity, these high MW proteins are highly immunogenic and have been shown by Western Blot to induce high titer of antibody [ 45 ]. Although ‘antigenic competition’ [ 46 ] in antivenom production has not yet been established, the presence of these proteins in the immunogen mix could possibly interfere with the production of antibodies specific against the lethal toxins of the venom as have been observed with other venoms [ 47 – 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Three crude venoms were included as immunogen because these venoms were available in very limited amounts at the time, and were not enough for the entire immunization program if they were prepared as TFs. Whether the small amount of high MW proteins of these 3 crude venoms had any inhibitory effect [ 47 – 49 ] or adjuvant effect [ 58 ] on the antibody production observed here is not known.…”

Section: Discussionmentioning

confidence: 99%

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A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia

et al. 2016

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Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a ‘pan-specific’ AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a ‘pan-specific’ AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund’s adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings were: a) The 9 TFs were shown to contain all of the venom toxins but were devoid of high MW proteins. When these TFs, together with the 3 crude venoms, were used as the immunogen, satisfactory ELISA antibody titers against homologous/heterologous venoms were obtained. b) The horse antiserum immunologically reacted with and neutralized the lethal effects of both the homologous and the 16 heterologous Asian/African elapid venoms tested. Thus, the use of TFs in place of crude venoms and the inclusion of a variety of elapid venoms in the immunogen mix resulted in antiserum with wide paraspecificity against elapid venoms from distant geographic areas. The antivenom prepared from this antiserum would be expected to be pan-specific and effective in treating envenomations by most elapids in many Asian countries. Due to economies of scale, the antivenom could be produced inexpensively and save many lives. This simple strategy and procedure could be readily adapted for the production of pan-specific antisera against elapids of other continents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia

et al. 2016

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“…alternatus (12.5%) and B . neuwiedi (12.5%), and consists of purified F(ab') 2 fragments generated by digestion with pepsin of ammonium sulfate-precipitated IgG molecules [ 33 ]. Experimental monospecific AB, AC, and AL antivenoms were prepared by the Industrial Division of Instituto Clodomiro Picado from plasma of horses subjected to a single round of immunization with venoms of Costa Rican adult B .…”

Section: Methodsmentioning

confidence: 99%

“…simus , and adult L . stenophrys , respectively, as described [ 33 ]. These monospecific antivenoms are also whole IgG preparations prepared by caprylic acid precipitation [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

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Cross-reactivity, antivenomics, and neutralization of toxic activities of Lachesis venoms by polyspecific and monospecific antivenoms

et al. 2017

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BackgroundBothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa.MethodsTo assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated.ResultsA conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged.ConclusionsDespite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming.General significanceThis study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.

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Animal Toxins

Bolon¹,

Heinz-Taheny²,

Yeung³

et al. 2023

Haschek and Rousseaux's Handbook of Toxicologic Pathology, Volume 3

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Lachesis stenophrys venom reduces the equine antibody response towards Bothrops asper venom used as co-immunogen in the production of polyspecific snake antivenom

Cited by 13 publications

References 26 publications

A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia

A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia

Cross-reactivity, antivenomics, and neutralization of toxic activities of Lachesis venoms by polyspecific and monospecific antivenoms

Animal Toxins

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