HisAK70: progress towards a vaccine against different forms of leishmaniosis

Abstract

BackgroundLeishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd.MethodsHere, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL.ResultsHisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model.ConclusionsThe results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.

Overview of dendritic cell‐based vaccine development for leishmaniasis

“…Vaccination of mice with this DNA vaccine resulted in very strong protection against host visceral and CL. It was demonstrated that murine livers were completely cleared from parasites following an infection challenge . In another study, Guha et al.…”

Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?

“…DNA vaccines are the more expressive in respect of the number of candidates explored, containing the simplest vaccine candidates: consist of usually non-adjuvanted plasmids (the "real DNA vaccines"). Similar to what was described for second-generation vaccines, both membrane (e.g., KMP-11 and gp63) and non-membrane antigens (e.g., NH, CPB, HSP70, and A2) were explored in the context of plasmid vaccine candidates ( Table 1), pre-clinically, using animal models for both CL and VL [37,51,55,85,86,90,[111][112][113][114][115][116][117][118]. Interestingly, many of the candidates tested as second-generation vaccines (and particularly those that have shown some degree of promise) were retested as DNA vaccines, either individually or in "multi-antigen" approaches (e.g., KMP-11, A2, LACK, and TSA+LmSTI1), showing the adoption of a rationale-based vaccine development [114].…”

Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis

“…Fused targets can also be created within DNA vaccines, and seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11, and HSP70) are encoded within the HisAK70 DNAvaccine (37). In the VL model, HisAK70-immunized mice exhibited many sterile hepatic granulomas associated with the resolution of hepatic parasite burdens, and in the CL model, spread of parasites to the viscera was completely inhibited in HisAK70-immunized mice.…”