PATRICK JACK SPENCER

PATRICK JACK SPENCER

(Fonte: Lattes)

Resumo

Possui graduação em Ciências Biológicas pela Universidade Presbiteriana Mackenzie (1991), mestrado em Tecnologia Nuclear pela Universidade de São Paulo (1995) e doutorado em Tecnologia Nuclear pela Universidade de São Paulo (2000) tendo sido bolsista sandwich no US Army Medical Research Institute for Infeccious Diseases (98-99). É responsável pelo Biotério de criação e manutenção de animais de laboratório do IPEN. Tem experiência na área de Bioquímica, com ênfase em Proteínas, atuando principalmente nos seguintes temas: veneno, proteínas, bothrops, irradiação e miotoxina.(Texto extraído do Currículo Lattes em 22 dez. 2021)

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Comparing traditional and toxin-oriented approaches towards antivenom production against Bitis arietans snake venom
2023 - GUIDOLIN, FELIPE R.; GODOI, KEMILY S. de; MEGALE, ANGELA A.A.; SILVA, CRISTIANE C.F. da; KODAMA, ROBERTO T.; CAJADO-CARVALHO, DANIELA; IWAI, LEO K.; SPENCER, PATRICK J.; PORTARO, FERNANDA C.V.; SILVA, WILMAR D. da
Accidents with snakes are responsible for about 32,000 deaths annually in sub-Saharan Africa, caused mostly by snakes from the genus Bitis, in particular Bitis arietans. B. arietans venom is composed of a complex mixture of toxins, mainly metalloproteases, serine proteases, phospholipases, lectins, and disintegrins. In this work, we compared two approaches to anti-B. arietans antivenom production: immunization with crude snake venom (“traditional approach”) and immunization with selected key toxins isolated from the snake venom (“toxin oriented” approach). Fractions from B. arietans venom were isolated by size exclusion chromatography. Crude venom and samples containing serine proteases or metalloproteases were selected for the immunization of BALB/c mice. Anti-B. arietans and anti-serine proteases plasmas showed a similar recognition profile and higher titers and affinity than the anti-metalloproteases plasma. Cross-recognition of other Bitis venoms was observed, but with low intensity. Although the plasma of all experimental groups inhibited the enzymatic activity of B. arietans venom in vitro, in vivo protection was not achieved. Our results have shown limitations in both approaches considered. Based on this, we proposed a model of polyclonal, species-specific, monovalent antivenoms that could be used as a base to produce customizable polyvalent sera for use in sub-Saharan Africa.
Anti-Metalloproteases
2023 - GODOI, KEMILY S. de; GUIDOLIN, FELIPE R.; PORTARO, FERNANDA C.V.; SPENCER, PATRICK J.; SILVA, WILMAR D. da
Bitis arietans is a medically important snake found in Sub-Saharan Africa. The envenomation is characterized by local and systemic effects, and the lack of antivenoms aggravates the treatment. This study aimed to identify venom toxins and develop antitoxins. The F2 fraction obtained from Bitis arietans venom (BaV) demonstrated the presence of several proteins in its composition, including metalloproteases. Titration assays carried out together with the immunization of mice demonstrated the development of anti-F2 fraction antibodies by the animals. The determination of the affinity of antibodies against different Bitis venoms was evaluated, revealing that only BaV had peptides recognized by anti-F2 fraction antibodies. In vivo analyses demonstrated the hemorrhagic capacity of the venom and the effectiveness of the antibodies in inhibiting up to 80% of the hemorrhage and 0% of the lethality caused by BaV. Together, the data indicate: (1) the prevalence of proteins that influence hemostasis and envenomation; (2) the effectiveness of antibodies in inhibiting specific activities of BaV; and (3) isolation and characterization of toxins can become crucial steps in the development of new alternative treatments. Thus, the results obtained help in understand
Antibodies as snakebite antivenoms
2022 - SILVA, WILMAR D. da; ANDRADE, SONIA A. de; MEGALE, ANGELA A.A.; SOUZA, DANIEL A. de; SANTANNA, OSVALDO A.; MAGNOLI, FABIO C.; GUIDOLIN, FELIPE R.; GODOI, KEMILY S.; SALADINI, LUCAS Y.; SPENCER, PATRICK J.; PORTARO, FERNANDA C.V.
Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab’)2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development.