A lentiviral vaccine expressing KMP11-HASPB fusion protein increases immune response to Leishmania major in BALB/C

Abstract

Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania-specific protein that antibodies are produced against it in the sera of Leishmania-infected individuals. Kinetoplastid membrane protein 11 (KMP11) is another Leishmania antigen and considered as the suitable candidate for vaccine development Leishmaniasis. It is a highly conserved surface protein expressed in both promastigotes and amastigotes. In this study, KMP11 and HASPB coding sequences were cloned into a pCDH-cGFP lentiviral vector as a fusion protein to be used as a DNA vaccine against L. major. The KMP11-HASPB fusion protein was successfully expressed as evidenced by RT-PCR and Western blot assays. The effect of the vaccine was determined by evaluating the level of IFN-γ, IL-10, IgG1, and IgG2a performed using ELISA as well as determining the parasite load after challenge with L. major in vaccinated mice. The results revealed that IFN-γ, IL-10, IgG1, and IgG2a significantly increased after vaccination using KMP11-HASPB-expressing lentiviruses in BALB/c mice. It is noteworthy that the level of IFN-γ and IgG2a was higher than that of IL-10 and IgG1, respectively, which indicates the activation Th1 cells, macrophages, and cellular immunity. Moreover, the parasite load in the spleen and lymph node of vaccinated mice after challenge was significantly lower than that of controls.

Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

“…In our previous study, immunogenicity evaluation of the whole protein of KMP11 and HASPB against L. major was successful in the BALB/c mice (14). Therefore, in this study, for the rst time, the immunogenicity of the KMP11 and HASPB as selected epitopes of the L-major was evaluated as a novel lentiviral multi-epitope vaccine.…”

“…In our previous studies, we found that the lentiviral vaccine containing the kinetoplastid membrane protein 11 (KMP11) and hydrophilic acylated surface protein B (HASPB) whole proteins are capable of stimulating the immune system in the BALB/c mice (14). Therefore, in this study, the immunogenic effects of the epitopes of these two antigens were investigated.…”

Vaccines for leishmaniasis and the implications of their development for American tegumentary leishmaniasis

“…145 A fusion of the kinetoplastid membrane protein 11 (KMP11) and hydrophilic acylated surface protein B (HASPB) genes was cloned into a lentiviral vector (pCDH-cGFP) that generated a protective response with significant increases in both pro-and antiinflammatory markers (IFN-γ and IgG2a versus IL-10 and IgG1). 146 The higher levels of IFN-γ and IgG2a indicated skewing toward a desirable Th1 response.…”

Investigation of Leish-111f Epitopes to Design a New Multi-epitope Vaccine Against Leishmania Major Using Immunoinformatics Approaches

“…Understanding the host defense mechanism against the parasite is essential in the production of an effective vaccine. Studies on leishmaniasis have shown that stimulation of cellular immunity is essential for defense against the parasite (8). Once the parasite enters the host, macrophages M1 or M2 play a key role in the parasite's defense or survival.…”