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

J Infect Dev Ctries. 2021 Sep 30;15(9):1328-1338. doi: 10.3855/jidc.14472.

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.

Keywords: Cysteine protease; DNA vaccine; Leishmania; Leishmania vaccine; Leishmaniasis; immunization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Humans
  • Interleukin-10 / blood
  • Leishmania / immunology*
  • Leishmaniasis, Cutaneous / blood
  • Leishmaniasis, Cutaneous / epidemiology
  • Leishmaniasis, Cutaneous / prevention & control*
  • Leishmaniasis, Visceral / blood
  • Leishmaniasis, Visceral / epidemiology
  • Leishmaniasis, Visceral / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Thailand / epidemiology
  • Vaccination
  • Vaccines, DNA / immunology*

Substances

  • IL10 protein, human
  • Vaccines, DNA
  • Interleukin-10