RESUMEN
Visceral leishmaniasis (VL) is caused by Leishmania infantum in the Mediterranean basin and affects primarily children and immunosuppressed individuals. Various strategies of vaccination have so far been examined by either protein or DNA without achievable complete protection against the disease. The live non-pathogenic lizard parasite, Leishmania tarentolae, expressing elected Leishmania antigens has recently provided a promising new approach as a safe and effective live vaccine candidate to prevent leishmaniasis. Here, we evaluated the immunoprotective potential of a live recombinant L. tarentolae expressing Lipophosphoglycan 3 (LPG3) antigen against L. infantum infection in BALB/c mice. Results indicated that the administration of live recombinant Leishmania produced a significant high level of IFN-γ accompanied by reduced levels of IL-10 as compared to wild-type parasites as live vaccine control, thus suggesting the induction of a Th1-type immune response in a mouse model of visceral leishmaniasis. Analysis of the IgG antibody response also showed high levels of IgG2a relative to IgG1 in sera of mice immunized with recombinant Leishmania parasites. However, immune responses elicited by this live vaccine conferred partial protection against infectious challenge. Therefore, further studies are required to increase its protective efficacy.
Asunto(s)
Leishmania infantum/inmunología , Vacunas contra la Leishmaniasis/inmunología , Leishmaniasis Visceral/inmunología , Proteínas Protozoarias/inmunología , Animales , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-10/inmunología , Interleucina-10/metabolismo , Leishmania infantum/fisiología , Vacunas contra la Leishmaniasis/administración & dosificación , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/prevención & control , Ratones Endogámicos BALB C , Proteínas Protozoarias/administración & dosificación , Proteínas Protozoarias/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/parasitología , Resultado del Tratamiento , Vacunación/métodosRESUMEN
Development of a protective antileishmanial vaccine is an urgent priority for successful control of different forms of leishmaniasis. The potential of a recombinant lipophosphoglycan 3 (rLPG3) expressed by Leishmania tarentolae was evaluated in combination with CpG oligodeoxynucleotides (CpG-ODN) as a Th1-promoting adjuvant against Leishmania infantum infection in BALB/c mice. First, mice were immunized subcutaneously with rLPG3 either alone or in combination with CpG-ODN. Next, the immunogenic and protective efficacies of this vaccine were analysed in immunized mice. It was observed that coadministration of rLPG3 with CpG-ODN led to enhance in a Th1 response to rLPG3 induced by itself as the IFN-γ production was promoted in association with the predominant presence of IgG2a antibodies in the sera. However, immunization with rLPG3 plus CpG-ODN induced partial protection against infectious challenge in BALB/c mice. Taken together, further studies are required to improve the protective efficacy using either more potent immune enhancers or vaccination strategies.
Asunto(s)
Glicoesfingolípidos/inmunología , Leishmania infantum/inmunología , Leishmaniasis/prevención & control , Oligodesoxirribonucleótidos/inmunología , Vacunas Antiprotozoos/inmunología , Adyuvantes Inmunológicos , Animales , Femenino , Inmunogenicidad Vacunal , Leishmaniasis/inmunología , Ratones , Ratones Endogámicos BALB CRESUMEN
Visceral leishmaniasis is a serious parasitic infection that the development of an effective vaccine is necessary to control the disease. Lipophosphoglycan 3 (LPG3) is essential for the synthesis of glycoconjugates as parasite virulence factors. In this study, we evaluated the immunogenicity of Leishmania infantum LPG3 gene as a DNA vaccine against murine visceral leishmaniasis. For this purpose, BALB/c mice were immunized subcutaneously with the DNA encoding LPG3 either alone or in combination with recombinant heat shock protein 70 (rHSP70). Next, its immunogenicity and protective efficacy were evaluated in the immunized mice. The results showed a mixed Th1/Th2 response following immunization, which was associated with the production of both IFN-γ and IL-10 by splenocytes compared with control groups but did not lead to reduction in the splenic parasite burden. Serum levels of IgG antibody isotypes indicated no significant difference between the LPG3 DNA and the empty vector. In addition, the co-administration of rHSP70 with the DNA vaccine offered no additive protective advantage on experimental infectious challenge. Thus, we propose to strengthen the immunogenic potential of L. infantum LPG3 in prime-boost approach with a powerful adjuvant to elicit a robust parasite-specific protective Th1 response.