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

Abstract

Leishmania amazonensis is the aetiological agent of a broad spectrum of leishmaniosis in South America. It can cause not only numerous cases of cutaneous leishmaniosis but also diffuse cutaneous leishmaniosis. Considering the diversity of parasite species causing different forms of the disease that coexist in the same region, it is desirable to develop a vaccine capable of eliciting cross-protection. We have previously described the use of HisAK70 DNA vaccine for immunization of mice to assess the induction of a resistant phenotype against Leishmania major and infantum infections. In this study, we extended its application in the murine model of infection by using L. amazonensis promastigotes. Our data revealed that 14 weeks post-infection, HisAK70-vaccinated mice showed key biomarkers of protection, such as higher iNOS/arginase activity, IFN-γ/IL-10, IFN-γ/IL-4, and GM-CSF/IL-10 ratios, in addition to an IgG2a-type response when compared to the control group. These findings correlated with the presentation of lower footpad swelling and parasite burdens in the immunized compared to the control mice. Overall, this study suggests that immunization with HisAK70 may be considered a suitable tool to combat leishmaniosis as it is able to induce a potent cellular immune response, which allows to control the infection caused by L. amazonensis.

Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way

“…In the present study, to obtain multiepitope peptides capable of strongly binding to human and mouse MHC class I and II molecules, we performed an in silico analysis of six Leishmania antigens (four core histones: H2A, H2B, H3, H4; A2 protein, and KMP-11) that had already been suggested to be effectively encoded as DNA vaccines against CL or VL in the murine model [ 33 , 42 , 43 ].…”

“…In this context, our group has worked with seven highly immunogenic Leishmania antigens (H2A, H2B, H3, H4, A2, KMP11, and HSP70) [ 27 , 28 , 29 , 30 , 33 ]. These antigens have been demonstrated to be able to induce partial protection against L. infantum , L. major and L. amazonensis infection, being encoded as DNA vaccines [ 33 , 43 ]. In addition, we have shown that HisAK70 DNA vaccination followed by an adoptive transfer of BMDCs pulsed with the HisAK70 polyprotein cocktail was successful against an ex vivo L. infantum challenge in dogs [ 34 ].…”

“…The immune resistance phenotype induced before the in vivo challenge was analyzed by measuring the ability of lymphocytes from immunized animals to confer killing activity to naïve BMDCs following the procedures as previously described [ 43 ]. A total of 400 cells per animal were counted by optical microscopy (Olympus BX41, Olympus, Tokio, Japan).…”

“…The percentage of infected cells and the mean number of intracellular amastigotes per infected cell were evaluated. The infection index (percentage of infected cells × number of parasites per infected cells) was also determined to account for the overall parasite load [ 43 ].…”

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

“…For example, the human immunodeficiency virus-1 (both as a prophylactic and an immunotherapeutic vaccine) ( 58 , 59 ), Zika virus ( 60 ), and Ebola virus vaccines ( 61 ) are currently in clinical trials. Comparatively, little progress has been made toward developing DNA vaccines against parasitic diseases, although several pre-clinical studies have shown promising results against hookworm infections ( 62 , 63 ), malaria ( 64 , 65 ), leishmaniasis ( 66 , 67 ), and schistosomiasis ( 68 , 69 ). Even though DNA vaccines offer several advantages when compared with recombinant vaccines, such as safety, improper protein folding and production cost, they have not been shown to be sufficient to induce a protective immune response ( 70 ).…”