Navegando por Autor "Bethony, Jeffrey Michael"

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    Antigenicity of a whole parasite vaccine as promising candidate against canine leishmaniasis.
    (2008) Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa; Lemos, Denise da Silveira; Martins Filho, Olindo Assis; Oliveira, Rodrigo Corrêa de; Bethony, Jeffrey Michael; Vale, André Macedo; Quetz, Josiane da Silva; Bueno, Lilian Lacerda; Silva, João Carlos França da; Nascimento, Evaldo do; Mayrink, Wilson; Fujiwara, Ricardo Toshio
    Human visceral leishmaniasis, one of the most important zoonoses, is caused by the protozoaLeishmania chagasi(syn. L. infantum ) and is present as a fatal disease common in South America and Europe where dogs and wild canids are the main reservoirs. A vaccine against visceral leishmaniasis would be an important tool in the control of this disease in dogs. Although the current strategies for vac-cination against leishmaniasis are based on the use of recombinant antigens, killed vaccines are still attractive in terms of stability of their biochemical composition and antigenicity, cost, and safety. Here we evaluate the immunogenicity of a whole parasite vaccine as a prom-ising candidate against canine leishmaniasis, demonstrated by cellular reactivity, changes in the cellular profile of the peripheral blood and by the differential production of immunoglobulins. Our results showed that immunization elicited mainly a strong cellular reactivity and increase in T-lymphocytes, particularly the subpopulation CD8 + that would be related to the control of tissue parasitism. In addi-tion, a higher production of anti- Leishmania total IgG, characterized by mixed isotypes profile (IgG1 and IgG2), was demonstrated.
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    Immunogenicity in dogs of three recombinant antigens (TSA, LeiF and LmSTI1) potential vaccine for canine visceral leishmaniasis.
    (2005) Fujiwara, Ricardo Toshio; Vale, André Macedo; Silva, João Carlos França da; Costa, Roberto Teodoro da; Quetz, Josiane da Silva; Martins Filho, Olindo Assis; Reis, Alexandre Barbosa; Oliveira, Rodrigo Corrêa de; Coelho, George Luiz Lins Machado; Bueno, Lilian Lacerda; Bethony, Jeffrey Michael; Frank, Glen; Nascimento, Evaldo do; Genaro, Odair; Mayrink, Wilson; Reed, Steven G.; Campos Neto, Antonio
    Control of canine visceral leishmaniasis (VL) remains a difficult and serious problem mostly because there is no reliable and effective vaccine available to prevent this disease. A mixture of three recombinant leishmanial antigens (TSA, LeIF and LmSTI1) encoded by three genes highly conserved in the Leishmania genus have been shown to induce excellent protection against infection in both murine and simian models of cutaneous leishmaniasis. A human clinical trial with these antigens is currently underway. Because of the high degree of conservation, these antigens might be useful vaccine candidates for VL as well. In the present study, using the dog model of the visceral disease, we evaluated the immunogenicity of these three antigens formulated with two different adjuvants, MPL-SE® and AdjuPrime®. The results were compared with a whole parasite vaccine formulated with BCG as the adjuvant. In order to investigate if sensitization with the recombinant antigens would result in recognition of the corresponding native parasite antigens upon infection, the animals were exposed for four weeks after the termination of the immunization protocol with the recombinant antigens to a low number of L. chagasi promastigotes, an etiological agent of VL. Immune response was evaluated by quantitative ELISA in the animal sera before and after exposure to the viable parasites. Both antigen specific IgG1 and IgG2 antibody levels were measured. Immunization of dogs with the recombinant antigens formulated in either MPL-SE® or AdjuPrime® resulted in high antibody levels particularly to LmSTI1. In addition, this immunization although to low levels, resulted in the development of antibody response to the whole parasite lysate. Importantly, experimental exposure with low numbers of culture forms of L. chagasi promastigotes caused a clear boost in the immune response to both the recombinant antigens and the corresponding native molecules. The boost response was predominantly of the IgG2 isotype in animals primed with the recombinant antigens plus MPL-SE®. In contrast, animals primed with the recombinant antigens formulated in AdjuPrime® as well as animals vaccinated with crude antigen preparation responded with mixed IgG1/IgG2 isotypes. These results point to the possible use of this antigen cocktail formulated with the adjuvant MPL-SE® in efficacy field trials against canine VL.