Phage-fused epitopes fromLeishmania infantumused as immunogenic vaccines confer partial protection againstLeishmania amazonensisinfection

Abstract

Two mimotopes of Leishmania infantum identified by phage display were evaluated as vaccine candidates in BALB/c mice against Leishmania amazonensis infection. The epitope-based immunogens, namely B10 and C01, presented as phage-fused peptides; were used without association of a Th1 adjuvant, and they were administered isolated or in combination into animals. Both clones showed a specific production of interferon-gamma (IFN-γ), interleukin-12 (IL-12) and granulocyte/macrophage colony-stimulating factor (GM-CSF) after in vitro spleen cells stimulation, and they were able to induce a partial protection against infection. Significant reductions of parasite load in the infected footpads, liver, spleen, bone marrow and paws' draining lymph nodes were observed in the immunized mice, in comparison with the control groups (saline, saponin, wild-type and non-relevant clones). Protection was associated with an IL-12-dependent production of IFN-γ, mediated mainly by CD8(+) T cells, against parasite proteins. Protected mice also presented low levels of IL-4 and IL-10, as well as increased levels of parasite-specific IgG2a antibodies. The association of both clones resulted in an improved protection in relation to their individual use. More importantly, the absence of adjuvant did not diminish the cross-protective efficacy against Leishmania spp. infection. This study describes for the first time two epitope-based immunogens selected by phage display technology against L. infantum infected dogs sera, which induced a partial protection in BALB/c mice infected with L. amazonensis.

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

“…Nevertheless, as observed, after the challenge, there was a production of specific anti-SLA antibodies. In BALB/c mice infected with L. amazonensis, the IL-4-dependent production of the IgG1 isotype is associated with disease progression [27,67,68], and the same behaviour is observed in control mice. These data show that non-immunized animals present a susceptible immune phenotype characterized by an inefficient humoral response leading to disease progression, whereas Th1 cytokines from HisAK70-immunized animals together with iNOS and IgG2a production induce a resistant immune phenotype controlling disease progression.…”

Cross‐protective efficacy from a immunogen firstly identified in Leishmania infantum against tegumentary leishmaniasis

“…GM‐CSF has played an important role in the activation, maturation and function of dendritic cells . In the present study, spleen cells from mice vaccinated with rLiHyT/saponin showed higher levels of parasite‐specific GM‐CSF, a molecule linked to the macrophages activation and resistance against infection caused by different Leishmania species, such as L. major , L. donovani , L. infantum and L. amazonensis . In addition, GM‐CSF is able to increase the immunogenicity of antigens that are vaccine candidates, when it was used in some disease models such as malaria , HIV and leishmaniasis .…”

Construction and immunogenicity of a recombinant swinepox virus expressing a multi-epitope peptide for porcine reproductive and respiratory syndrome virus

“…Peptide mimics of linear and discontinuous protein epitopes, as well as other non-protein antigens, can be affinity purified from RPLs30. The peptide epitope mimics (i.e., mimotopes) used as immunogens are a promising tool for vaccine design, and an efficient means of stimulating the antibody response to native antigens, and providing protection against infection in vivo 31.…”