Phase 1 Study of an Inactivated Vaccine against American Tegumentary Leishmaniasis in Normal Volunteers in Brazil

Marzochi, Keyla Belízia Feldman; Marzochi, Mauro Célio de Almeida; Silva, Aline F.; Grativol, Neiva; Duarte, Rosemere; Confort, Eliame Mouta; Modabber, Farrokh

doi:10.1590/s0074-02761998000200014

Cited by 50 publications

(34 citation statements)

References 22 publications

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“…Extensive vaccination trials in Brazil and Ecuador against cutaneous leishmaniasis in humans have demonstrated that a cocktail of five killed Leishmania stocks or a single strain of L. amazonensis induces protection from natural infection [1,13,23,32]. However, to date, the protection efficacy of these or other vaccines in dogs against visceral leishmaniasis is highly controversial [15,28,33,34].…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity in dogs of three recombinant antigens (TSA, LeIF and LmSTI1) potential vaccine candidates for canine visceral leishmaniasis

et al. 2005

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-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

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Section: Discussionmentioning

confidence: 99%

Immunogenicity in dogs of three recombinant antigens (TSA, LeIF and LmSTI1) potential vaccine candidates for canine visceral leishmaniasis

et al. 2005

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“…Classically, a positive MST is an indicator of previous contact with the parasite through natural inoculation after the bite of the sandfly. Alternatively, MST positivity can be the result of immunity acquired by vaccination (Mayrink et al 1979, Marzochi et al 1998, or nonspecific reactions to the merthiolate or phenol used in the MST as a preservative (Marzochi et al 1998, Fagundes et al 2003, 2007. In some cases, the nonspecific reaction was found to be morphologically identical to a classical positive MST (Marzochi et al 1998, Fagundes et al 2007), and it was not possible to discriminate between a false-positive MST due to merthiolate hypersensitivity and a true positive MST result.…”

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confidence: 99%

First encounter of subclinical human Leishmania (Viannia) infection in State of Rio Grande do Sul, Brazil

Fagundes

Marzochi

Fernandes³

et al. 2007

Mem. Inst. Oswaldo Cruz

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“…Associated with healing was resistance to subsequent challenge with an appropriate dose of homologous parasites. Studies with the vervet monkey model for cutaneous leishmaniasis have demonstrated that resistance to leishmaniasis in this model is correlated with increased production of gamma interferon (IFN-␥) and strong delayedtype hypersensitivity (DTH) responses (9, 25), similar to those seen in human patients with cutaneous leishmaniasis.Ongoing human vaccine studies against cutaneous leishmaniasis with newly developed vaccines (killed Leishmania parasites plus Mycobacterium bovis BCG) have achieved encouraging results, although the protection obtained has not been outstanding (3,18,19,30). Thus, additional studies to optimize protection are required.…”

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confidence: 99%

“…Ongoing human vaccine studies against cutaneous leishmaniasis with newly developed vaccines (killed Leishmania parasites plus Mycobacterium bovis BCG) have achieved encouraging results, although the protection obtained has not been outstanding (3,18,19,30). Thus, additional studies to optimize protection are required.…”

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confidence: 99%

Vervet Monkeys Vaccinated with KilledLeishmania majorParasites and Interleukin-12 Develop a Type 1 Immune Response but Are Not Protected against Challenge Infection

et al. 2001

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Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave disfiguring scars. Infections in mice have demonstrated that leishmanial vaccines that include interleukin-12 (IL-12) as an adjuvant are able to induce protective immunity. In this study, we assessed the safety, immunopotency, and adjuvant potential of two doses of IL-12 when used with a killed L. major vaccine in vervet monkeys. The induction of cell-mediated immunity following vaccination was determined by measuring delayed-type hypersensitivity, in vitro lymphocyte proliferation, and gamma interferon (IFN-␥) production. Protection was assessed by challenging the animals with L. major parasites and monitoring the course of infection. At low doses of IL-12 (10 g), a small increase in the parameters of cell-mediated immunity was observed, relative to those in animals that received antigen without IL-12. However, none of these animals were protected against a challenge infection. At higher doses of IL-12 (30 g), a substantial increase in Leishmania-specific immune responses was observed, and monkeys immunized with antigen and IL-12 exhibited an IFN-␥ response that was as great as that in animals that had resolved a primary infection and were immune. Nevertheless, despite the presence of correlates of protection, the disease course was only slightly altered, and protection was low compared to that in self-cured monkeys. These data suggest that protection against leishmaniasis may require more than the activation of Leishmania-specific IFN-␥-producing T cells, which has important implications for designing a vaccine against leishmaniasis.Cutaneous leishmaniasis is a disease caused by obligate intracellular protozoa of the genus Leishmania and is characterized by cutaneous lesions that can be self-resolving with life-long immunity or chronic when accompanied by defective cellular immune responses (27). The disease is prevalent in many tropical and subtropical regions of the world, where it is transmitted via the bite of the sand fly. Treatment for leishmaniasis often involves the use of high doses of pentavalent antimony compounds or various formulations of amphotericin B. However, the increasing prevalence of drug-resistant organisms and the tendency for patients to relapse after an initially successive regimen of chemotherapy underscore the need for an effective prophylactic vaccine (27).Efforts towards vaccine development have involved both animal model studies and human research. The vervet monkey is an excellent animal model for studying Leishmania major infection (4,11,17,(23)(24)(25)27). Similar to many human patients with leishmaniasis, the vervet monkey has been shown to undergo spontaneous cure following both natural and experimental infection with L. major. Associated with healing was resistance to subsequent challenge with an appropriate dose of homologous parasites. Studies with the vervet monkey model for cutaneous leishmaniasis have demonstrated that resistance to leishmaniasis in this model is correlated w...

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Phase 1 Study of an Inactivated Vaccine against American Tegumentary Leishmaniasis in Normal Volunteers in Brazil

Cited by 50 publications

References 22 publications

Immunogenicity in dogs of three recombinant antigens (TSA, LeIF and LmSTI1) potential vaccine candidates for canine visceral leishmaniasis

Immunogenicity in dogs of three recombinant antigens (TSA, LeIF and LmSTI1) potential vaccine candidates for canine visceral leishmaniasis

First encounter of subclinical human Leishmania (Viannia) infection in State of Rio Grande do Sul, Brazil

Vervet Monkeys Vaccinated with KilledLeishmania majorParasites and Interleukin-12 Develop a Type 1 Immune Response but Are Not Protected against Challenge Infection

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