Gerbu adjuvant modulates the immune response and thus the course of infection in C56BL/6 mice immunised with Echinococcus multilocularis rec14-3-3 protein

Abstract

Vaccination with Echinococcus multilocularis 14-3-3 protein can protect mice against primary E. multilocularis infection. The present study investigated the efficacy and efficiency of the adjuvant muramyl dipeptide Gerbu, alone or together with recombinant 14-3-3 protein, to modulate the course of secondary E. multilocularis infection in C56BL/6 mice. The application of Gerbu alone already resulted in a parasite weight reduction when compared with infected control mice, while rec14-3-3 did not add to this effect. Immunological parameters were concurrently assessed with a mixed cell reaction including bone marrow-derived dendritic cells (BMDCs) together with lymph node cells from mice with or without immunisation and/or infection. While mice having received Gerbu adjuvant were found to highly proliferate in response to co-cultivation with 14-3-3-stimulated bone marrow dendritic cells, a sensitisation of BMDCs with vesicle fluid (VF) antigen lead to a striking decrease of the lymphoproliferative response in comparison to that of control mice, raising the hypothesis that immunosuppressive components may be part of this VF-antigen. Anti-14-3-3 antibody production was only found in those mice that had been previously 14-3-3-immunised, whereas all other only-infected mice failed to produce such antibodies. Conclusively, Gerbu adjuvant appears to directly generate a non-specific immune response that contributes to the control of the metacestode growth, putatively in association with a BMDC activity suppressed by components of the VF-antigen.

Immunization of rhesus macaques with Echinococcus multilocularis recombinant 14-3-3 antigen leads to specific antibody response

“…This observation is in line with the results of previous experiments in mice confirming the immunogenicity of the recombinant Em14-3-3 (Siles-Lucas et al 2003; Margos and Gottstein 2010). The kinetics of the antibody levels in the five vaccinated monkeys as well as in the control animal are shown in Figs.…”

“…In previous studies, vaccinated mice were challenged orally with E. multilocularis eggs (primary infection) and intraperitoneal inoculation of metacestode tissue (secondary infection), respectively, with a subsequent quantitative assessment of metacestode proliferation (Müller-Schollenberger et al 2001; Gauci et al 2002; Siles-Lucas et al 2003; Margos and Gottstein 2010). The seroconversion induced by vaccination alone is not necessarily a criterion for the efficacy of the immunisation.…”

Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen

“…It was reported in a previous study that administration of saponin alone also gave a limited non-specific protection against secondary AE in mice. Similarly, other adjuvants such as CpG oligodeoxynucleotides [ 30 ] (CpG ODN), Freund’s complete/Incomplete adjuvants (CFA/IFA) [ 30 ], Gerbu [ 74 ] or cholera toxin subunit B (CTB) [ 75 ] have also been shown to exhibit non-specific protection against larval or adult stages of E . multilocularis .…”

In vitroinduction of lymph node cell proliferation by mouse bone marrow dendritic cells following stimulation with differentEchinococcus multilocularisantigens

“…That 'resistance' is increased upon stimulation of the cellular immune response was shown with the administration of Bacille Calmette Guérin (BCG) reagent (Rau & Tanner, 1975), and more recently with Gerbu-adjuvans (Margos & Gottstein, 2010;Vuitton, 2003). In several past experiments, E. multilocularis was suggested to directly inhibit and/or modulate the immune system either by cell -cell contact or by metabolizing active products.…”