Dataset Information

Immune Mechanisms Involved in Schistosoma mansoni-Cathepsin B Vaccine Induced Protection in Mice.

ABSTRACT: A vaccine against schistosomiasis would contribute to a long-lasting decrease in disease spectrum and transmission. Our previous protection studies in mice using Schistosoma mansoni Cathepsin B (Sm-Cathepsin B) resulted in 59 and 60% worm burden reduction with CpG oligodeoxynucleotides and Montanide ISA720 VG as adjuvants, respectively. While both formulations resulted in significant protection in a mouse model of schistosomiasis, the elicited immune responses differed. Therefore, in this study, we aimed to decipher the mechanisms involved in Sm-Cathepsin B vaccine-mediated protection. We performed in vitro killing assays using schistosomula stage parasites as targets for lung-derived leukocytes and serum obtained from mice immunized with Sm-Cathepsin B adjuvanted with either Montanide ISA 720 VG or CpG and from non-vaccinated controls. Lung cells and immune sera from the Sm-Cathepsin B?+?Montanide group induced the highest killing (63%) suggesting the importance of antibodies in cell-mediated parasite killing. By contrast, incubation with lung cells from Sm-Cathepsin B?+?CpG immunized animals induced significant parasite killing (53%) independent of the addition of immune serum. Significant parasite killing was also observed in the animals immunized with Sm-Cathepsin B alone (41%). For the Sm-Cathepsin B?+?Montanide group, the high level killing effect was lost after the depletion of CD4+ T cells or natural killer (NK) cells from the lung cell preparation. For the Sm-Cathepsin B?+?CpG group, high parasite killing was lost after CD8+ T cell depletion, and a reduction to 39% was observed upon depletion of NK cells. Finally, the parasite killing in the Sm-Cathepsin B alone group was lost after the depletion of CD4+ T cells. Our results demonstrate how the different Sm-Cathepsin B formulations influence the immune mechanisms involved in parasite killing and protection against schistosomiasis.

SUBMITTER: Ricciardi A

PROVIDER: S-EPMC6068236 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immune Mechanisms Involved in <i>Schistosoma mansoni</i>-Cathepsin B Vaccine Induced Protection in Mice.

Ricciardi Alessandra A Zelt Nicholas H NH Visitsunthorn Kittipos K Dalton John P JP Ndao Momar M

Frontiers in immunology 20180725

A vaccine against schistosomiasis would contribute to a long-lasting decrease in disease spectrum and transmission. Our previous protection studies in mice using <i>Schistosoma mansoni</i> Cathepsin B (Sm-Cathepsin B) resulted in 59 and 60% worm burden reduction with CpG oligodeoxynucleotides and Montanide ISA720 VG as adjuvants, respectively. While both formulations resulted in significant protection in a mouse model of schistosomiasis, the elicited immune responses differed. Therefore, in this ...[more]

PMID: 30090103

Similar Datasets

Project description:Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual's quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission.Our group has chosen Schistosoma mansoni (Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels.The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60%, 6%, and 56%, respectively in immunized animals compared to controls (P = 0.0002, P < 0.0001, P = 0.0009, respectively). Immunizations with the vaccine elicited robust production of Sm-cathepsin B specific antibodies (endpoint titers = 122,880). Both antigen-specific IgG1 and IgG2c titers were observed, with the former having more elevated titers. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, secreted higher levels of key Th1 cytokines, IFN-?, IL-12, and TNF-?, as well as the Th2 cytokines IL-5 and IL-4 when stimulated with recombinant Sm-cathepsin B. The Th17 cytokine IL-17, the chemokine CCL5, and the growth factor GM-CSF were also significantly increased in the immunized animals compared to the controls.The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.

Dataset Information

Immune Mechanisms Involved in Schistosoma mansoni-Cathepsin B Vaccine Induced Protection in Mice.

Publications

Immune Mechanisms Involved in <i>Schistosoma mansoni</i>-Cathepsin B Vaccine Induced Protection in Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets