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

Abstract

E. multilocularis (Em) is the etiologic agent of alveolar echinococcosis (AE), a severe and potentially fatal disease, primarily affecting the liver of and occurring in aberrant intermediate hosts, e.g., humans and non-human primates. Due to increasing numbers of spontaneous cases of AE in the Old World monkey colonies of the German Primate Center, the question arose as to whether vaccination of non-human primates may represent a useful prophylactic approach. In this pilot study, the recombinant antigen Em14-3-3, which has provided a 97 % protection against E. multilocularis challenge infection in rodent models, was used for the first time to immunize rhesus macaques. In order to increase immunogenicity, the antigen was formulated with different adjuvants including Quil A®, aluminum hydroxide (alum), and muramyl dipeptide (MDP). Also, different vaccination regimens were tested. All vaccinated animals developed antigen-specific antibodies. While Quil A® induced a local adverse reaction, alum proved to be the most potent adjuvant in terms of induced antibody levels, longevity as well as tolerability. In conclusion, our pilot study demonstrated that recombinant Em14-3-3 is safe and immunogenic in rhesus monkeys. As a next step, efficacy of the vaccination remains to be explored.

Extracellular vesicles from Echinococcus granulosus larval stage: Isolation, characterization and uptake by dendritic cells

“…In our proteomics data, we found 14-3-3 proteins which have been reported to provide 97% protection against E . multilocularis challenge infection in rodent and the production of a specific humoral response in rhesus macaque models, respectively [86, 87], the endophilin B1, which is highly expressed in the tegument of Taeniidae metacestodes and responsible for a strong immune recognition in sera from patients with cystic and alveolar echinococcosis and chronic neurocysticercosis [88], antigen 5, an immuno-dominant serine-protease with heparan sulphate proteoglycan- and calcium-binding sites, and antigen P-29 immunologically related to antigen 5 used as a marker for post-surgery surveillance of cystic echinococcosis patients [89, 90]. Antigen 5 is highly immunogenic in human infections although its highly cross-reactive glycan moieties may involve a parasite evasion mechanism [91–95].…”

Broad Protection of Pigs against Heterologous PRRSV Strains by a GP5-Mosaic DNA Vaccine Prime/GP5-Mosaic rVaccinia (VACV) Vaccine Boost

“…This type of prime-boost regime has previously been demonstrated to increase vaccination efficacy substantially [51,52]. In addition, Quil-A ® , used as adjuvant for the priming of the GP5-Mosaic DNA vaccine, was previously shown to further increase the immune responses [53][54][55]. Therefore, the prime-boost vaccination regime used here for testing GP5-Mosaic vaccine efficacy, in terms of broad protection, proved appropriate for testing the hypothesis.…”

Designing a Recombinant Multi-Epitope Antigen of Echinococ-cus granulosus to Diagnose Human Cystic Echinococcosis

“…Recombinant proteins and peptides are more reliable for immunodiagnostic and vaccine purposes than natural antigens (30)(31)(32). Native AgB was more sensitive than recombinant AgB, with sensitivity of 80 and 68, respectively, but the specificity of recombinant AgB was more than native AgB (33).…”