Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition

Pessenda, Gabriela; Silva, Luciano C.; Campos, Laa; Pacello, Elenice M.; Pucca, Manuela Berto; Martinez, Edson Zangiacomi; Barbosa, José Elpídio

doi:10.1016/j.toxicon.2016.01.062

Cited by 18 publications

(15 citation statements)

References 33 publications

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“…Afribumab 1 and 2 presented the capacity to inhibit bee venom hemolysis (0.5 μg) in vitro at a mass to mass ratio of 1:1:1 (bee venom:Afribumab 1:Afribumab 2). Using mice challenged with 2 LD 50 s of bee venom (corresponding to 9.484 μg/g of bee venom), the combination of Afribumabs 1 and 2 with the same ratio of 1:1:1 was demonstrated to reduce edema and prolong mouse survival for more than 400 min (compared to around 100 min when the mice were only challenged with 2 LD 50 s of bee venom) (191). Combined, these studies demonstrated that phage display technology can be an effective methodology for selecting antibodies with specificity against non-immunogenic components of bee venom (e.g., melittin).…”

Section: Next-generation Antivenom Therapymentioning

confidence: 99%

Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy

et al. 2019

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Honey bees can be found all around the world and fulfill key pollination roles within their natural ecosystems, as well as in agriculture. Most species are typically docile, and most interactions between humans and bees are unproblematic, despite their ability to inject a complex venom into their victims as a defensive mechanism. Nevertheless, incidences of bee stings have been on the rise since the accidental release of Africanized bees to Brazil in 1956 and their subsequent spread across the Americas. These bee hybrids are more aggressive and are prone to attack, presenting a significant healthcare burden to the countries they have colonized. To date, treatment of such stings typically focuses on controlling potential allergic reactions, as no specific antivenoms against bee venom currently exist. Researchers have investigated the possibility of developing bee antivenoms, but this has been complicated by the very low immunogenicity of the key bee toxins, which fail to induce a strong antibody response in the immunized animals. However, with current cutting-edge technologies, such as phage display, alongside the rise of monoclonal antibody therapeutics, the development of a recombinant bee antivenom is achievable, and promising results towards this goal have been reported in recent years. Here, current knowledge on the venom biology of Africanized bees and current treatment options against bee envenoming are reviewed. Additionally, recent developments within next-generation bee antivenoms are presented and discussed.

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Section: Next-generation Antivenom Therapymentioning

confidence: 99%

Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy

et al. 2019

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“…Finally, phage display selection has also been employed to discover antibody fragments against bee venom toxins [ 59 ]. In a study by Pessenda et al, the human scFv library, Griffin.1, was used to find scFvs against melittin and phospholipase A 2 from the Africanized bee Apis mellifera .…”

Section: Selected Examples Of the Use Of Antibody Phage Display Sementioning

confidence: 99%

“…Additionally, prolongation of survival was observed when mice were subjected to lethal doses of venom pre-incubated with the scFvs. However, full protection against lethality was not observed [ 59 ].…”

Section: Selected Examples Of the Use Of Antibody Phage Display Sementioning

confidence: 99%

Basics of Antibody Phage Display Technology

Ledsgaard

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Karatt-Vellatt³

et al. 2018

Toxins

178

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Antibody discovery has become increasingly important in almost all areas of modern medicine. Different antibody discovery approaches exist, but one that has gained increasing interest in the field of toxinology and antivenom research is phage display technology. In this review, the lifecycle of the M13 phage and the basics of phage display technology are presented together with important factors influencing the success rates of phage display experiments. Moreover, the pros and cons of different antigen display methods and the use of naïve versus immunized phage display antibody libraries is discussed, and selected examples from the field of antivenom research are highlighted. This review thus provides in-depth knowledge on the principles and use of phage display technology with a special focus on discovery of antibodies that target animal toxins.

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“…A combination of two of the resulting scFvs was reported to inhibit myotoxic effects in vivo and prolonged survival of mice in lethality assays, where venom and scFvs were preincubated prior to administration. Since these first discoveries of human monoclonal antibody fragments against animal toxins, phage display technology has been used to discover human monoclonal antibody fragments against toxins from other snakes (134–136), scorpions (128, 137), and bees (129, 138). To the best of our knowledge, no human monoclonal antibody fragment has yet been discovered against a spider toxin using phage display selection.…”

Section: Advances In Antivenom Researchmentioning

confidence: 99%

History of Envenoming Therapy and Current Perspectives

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Each year, millions of humans fall victim to animal envenomings, which may either be deadly or cause permanent disability to the effected individuals. The Nobel Prize-winning discovery of serum therapy for the treatment of bacterial infections (tetanus and diphtheria) paved the way for the introduction of antivenom therapies for envenomings caused by venomous animals. These antivenoms are based on polyclonal antibodies derived from the plasma of hyperimmunized animals and remain the only specific treatment against animal envenomings. Following the initial development of serum therapy for snakebite envenoming by French scientists in 1894, other countries with high incidences of animal envenomings, including Brazil, Australia, South Africa, Costa Rica, and Mexico, started taking up antivenom production against local venomous animals over the course of the twentieth century. These undertakings revolutionized envenoming therapy and have saved innumerous patients worldwide during the last 100 years. This review describes in detail the above-mentioned historical events surrounding the discovery and the application of serum therapy for envenomings, as well as it provides an overview of important developments and scientific breakthroughs that were of importance for antibody-based therapies in general. This begins with discoveries concerning the characterization of antibodies, including the events leading up to the elucidation of the antibody structure. These discoveries further paved the way for other milestones in antibody-based therapies, such as the introduction of hybridoma technology in 1975. Hybridoma technology enabled the expression and isolation of monoclonal antibodies, which in turn formed the basis for the development of phage display technology and transgenic mice, which can be harnessed to directly obtain fully human monoclonal antibodies. These developments were driven by the ultimate goal of producing potent neutralizing monoclonal antibodies with optimal pharmacokinetic properties and low immunogenicity. This review then provides an outline of the most recent achievements in antivenom research, which include the application of new biotechnologies, the development of the first human monoclonal antibodies that can neutralize animal toxins, and efforts toward creating fully recombinant antivenoms. Lastly, future perspectives in the field of envenoming therapies are discussed, including rational engineering of antibody cross-reactivity and the use of oligoclonal antibody mixtures.

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Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition

Cited by 18 publications

References 33 publications

Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy

Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy

Basics of Antibody Phage Display Technology

History of Envenoming Therapy and Current Perspectives

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