Immunogenicity and potential protection of DNA vaccine of Leishmania martiniquensis against Leishmania infection in mice

Abstract

Introduction: In Thailand, Leishmania martiniquensis is the predominant species causing cutaneous and visceral leishmaniasis. Its incidence has been increasing among immunocompetent and immunocompromised hosts. We developed a prototype DNA vaccine using a partial consensus sequence of the cysteine protease B (cpb) gene derived from L. martiniquensis from Thai patients.
 Methodology: The laboratory inbred strain of albino BALB/c mice were immunized intramuscularly three times at 2-week intervals (weeks 0, 2, and 4) with cpb plasmid DNA (pcDNA_cpb) with or without the adjuvant, monoolein (pcDNA_cpb-MO). Mice were challenged at week 6 with L. martiniquensis promastigotes. Sera were analysed for IgG1, IgG2a, interferon gamma and interleukin 10 (IFN-γ and IL-10, respectively) levels at weeks 0, 4, and 9. Additionally, livers and spleens were also analysed for parasite burden using immunohistochemistry and real-time polymerase chain (qPCR) assays.
 Results: Three weeks after promastigote challenge, vaccinated mice showed significantly increased levels of IgG2a and IFN-γ while IL-10 level was significantly reduced when compared with those in the control group (p < 0.01). Parasite burden in the livers and spleens of vaccinated mice significantly decreased. In addition, a significant increase in mature granuloma formation in the livers when compared with those of the control group (p < 0.05) was found, indicating increased T-helper cells (Th1)-induced inflammation and destruction of amastigotes. Monoolein produced a booster effect to enhance the mouse Th1 protective immunity.
 Conclusions: The prototype DNA vaccine could induce a Th1 immune response that conferred potential protection to the L. martiniquensis promastigote challenge in BALB/c mice.

Immunogenicity and protective efficacy of tuzin protein as a vaccine candidate in Leishmania donovani-infected BALB/c mice

“…Heat-killed Leishmania parasites coupled with different adjuvants significantly increased the production of IgG2a, indicating the generation of a protective Th1 response ( 61 ). A DNA vaccine containing cysteine protease B (cpb) gene or tuzin gene-vaccinated mice showed significantly increased levels of IgG2a and IFN-γ, while the IL-10 level was significantly reduced when compared with the control group ( 31 , 62 ). DNA plasmid (DNA LiHyP) or recombinant protein (rLiHyP) was also associated with high IgG2a antibodies and low IgG1 antibodies ( 63 ).…”

“…Leishmania amastigote-specific hypothetical protein (rLiHyJ and rLiHyG) plus saponin as an adjuvant or DNA vaccine induced higher IFN-g production, mainly by CD8 + T cells, while rLiHyJ/saponin stimulated the production of this cytokine, mainly by CD4 + T cells, and reduced the parasite load when compared with the controls (12,13). Mice immunized with plasmid DNA containing cysteine protease B (cpb) from L. martiniquensis showed significantly decreased parasite burden in the livers and spleens and increased levels of IgG2a and IFN-g, while the IL-10 level was significantly reduced (Aunguldee et al, 2021). Mice immunized with the L. donovani protein disulfide isomerase-DNA construct were found to have induced Th1and Th17-dependent immune response and T-cell proliferation (14).…”

Leishmania Vaccines: the Current Situation with Its Promising Aspect for the Future

“…DNA vaccines are safe because they do not contain any pathogenic organisms that may revert virulence [ 79 ]. They also efficiently induce interferon-gamma production and dendritic cell activation, which protects against Leishmania infection [ 80 ].…”