Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a Therapeutic Vaccine?

Abstract

BackgroundAmong animal models of schistosomiasis, the rhesus macaque is unique in that an infection establishes but egg excretion rapidly diminishes, potentially due to loss of adult worms from the portal system via shunts or death by immune attack.Principal FindingsTo investigate this, six rhesus macaques were exposed to Schistosoma mansoni cercariae and the infection monitored until portal perfusion at 18 weeks. Despite a wide variation in worm numbers recovered, fecal egg output and circulating antigen levels indicated that a substantial population had established in all animals. Half the macaques had portal hypertension but only one had portacaval shunts, ruling out translocation to the lungs as the reason for loss of adult burden. Many worms had a shrunken and pallid appearance, with degenerative changes in intestines and reproductive organs. Tegument, gut epithelia and muscles appeared cytologically intact but the parenchyma was virtually devoid of content. An early and intense IgG production correlated with low worm burden at perfusion, and blood-feeding worms cultured in the presence of serum from these animals had stunted growth. Using immunoproteomics, gut digestive enzymes, tegument surface hydrolases and antioxidant enzymes were identified as targets of IgG in the high responder animals.SignificanceIt appears that worms starve to death after cessation of blood feeding, as a result of antibody-mediated processes. We suggest that proteins in the three categories above, formulated to trigger the appropriate mechanisms operating in rhesus macaques, would have both prophylactic and therapeutic potential as a human vaccine.

Sm‐p80–Based DNA Vaccine Provides Baboons with Levels of Protection againstSchistosomamansoniInfection Comparable to Those Achieved by the Irradiated Cercarial Vaccine

“…Similar to previous studies [14], in present experiments, IgE was also not detectable in vaccinated animals. As recorded in this study, early emergence with short lives of IgM responses and very low or undetectable levels of IgE were also observed in the “self-curing” S. mansoni -rhesus macaque model [41]. Cumulatively our data on Sm-p80 specific humoral responses indicate that a mixed Th1/Th2 type of priming was achieved following vaccination with Sm-p80-VR1020 vaccine.…”

Evaluation of the immune response and protective efficacy of Schistosoma mansoni Cathepsin B in mice using CpG dinucleotides as adjuvant

“…The antibodies specific for Sm-Cathepsin B may be performing a neutralizing task; thus, blocking nutrient uptake and leading to parasite starvation. Immunoproteomic studies concerning schistosomiasis self-cure in rhesus macaques revealed that gut digestive enzymes were common IgG targets in high responder animals [40]. This observation strengthens the potential role of Sm-Cathepsin B specific antibodies in protection.…”

Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium

“…Sera obtained from donor immunized mice and baboons have been shown to protect recipients against subsequent schistosome challenge when passively transferred (Byram et al 1979; Doenhoff et al 1979; Mangold and Dean 1986; Melo et al 2014; Torben et al 2011). Studies utilizing schistosome non- and/or semi-permissive host such as rats have shown that resistance to schistosome infections as well as mechanism of schistosome killing are almost entirely humoral mediated by high IgG antibodies (Knopf et al 1977; Wilson et al 2008). Our group have also demonstrated the potential effector role of antibody dependent complement mediated cytotoxicity (ADCC) in schistosome killing (Torben et al 2012).…”