Antibody Responses to Sarcoptes scabiei Apolipoprotein in a Porcine Model: Relevance to Immunodiagnosis of Recent Infection

Abstract

No commercial immunodiagnostic tests for human scabies are currently available, and existing animal tests are not sufficiently sensitive. The recombinant Sarcoptes scabiei apolipoprotein antigen Sar s 14.3 is a promising immunodiagnostic, eliciting high levels of IgE and IgG in infected people. Limited data are available regarding the temporal development of antibodies to Sar s 14.3, an issue of relevance in terms of immunodiagnosis. We utilised a porcine model to prospectively compare specific antibody responses to a primary infestation by ELISA, to Sar s 14.3 and to S. scabiei whole mite antigen extract (WMA). Differences in the antibody profile between antigens were apparent, with Sar s 14.3 responses detected earlier, and declining significantly after peak infestation compared to WMA. Both antigens resulted in >90% diagnostic sensitivity from weeks 8–16 post infestation. These data provide important information on the temporal development of humoral immune responses in scabies and further supports the development of recombinant antigen based immunodiagnostic tests for recent scabies infestations.

The immunology of the porcine skin and its value as a model for human skin

“…This includes studies on wound healing (Ansell et al, 2012;Jung et al, 2013;Sullivan et al, 2001), burns (Abdullahi et al, 2014;Sheu et al, 2014), transdermal penetration, delivery and toxicology (Barbero and Frasch, 2009;Godin and Touitou, 2007;Mahl et al, 2006;Simon and Maibach, 2000;Yu et al, 2013), infectious diseases (Mounsey et al, 2010;Rampton et al, 2013;San Mateo et al, 1999), radiation and UVB impact (Agay et al, 2010;Brozyna et al, 2009;Smirnova et al, 2014), snake venom (Imkhieo et al, 2009) and taser (Jenkins et al, 2013) assessments, as well as stem cell research (Hao et al, 2009;Zhao et al, 2012). The pig was also employed as a model for experimentally induced allergic contact dermatitis, revealing similarities to human with respect to clinical, histological and immunohistological features (Vana and Meingassner, 2000).…”

Crusted scabies is associated with increased IL‐17 secretion by skin T cells

“…These infected pigs were not exposed to dexamethasone to avoid confounding interpretation of changes occurring due to mite infestation and those due to corticosteroid immunosuppression alone. Based on previous trials (11), a proportion of the infected pigs were expected to develop hyperkeratotic mange with high mite burdens, akin to crusted scabies, reaching maximum clinical severity between 12 and 16 weeks, whereas others would maintain infestation with few clinical signs and low mite burden (akin to ordinary scabies).…”

“…In individuals with crusted scabies, the main skininfiltrating T cells have been reported to be CD8 + T cells (4). It has been suggested that a Th2-biased immune response in S. scabiei infestation may account for the development of crusted scabies (6,11). Peripheral blood mononuclear cells (PBMCs) isolated from patients with crusted scabies secreted higher levels of IL-4, IL-5 and IL-13, and lower levels of IFNc, compared to those of ordinary scabies patients; levels of total and antigenspecific IgE are also higher in crusted scabies patients (12)(13)(14)(15).…”

“…Animal models provide the opportunity to investigate the immunopathologic mechanisms of scabies development, and a tractable porcine model of scabies has been recently developed (11,16). When infested with S. scabiei var.…”

“…In this porcine model, the corticosteroid dexamethasone is commonly utilized to induce crusted scabies and provide large numbers of mites for biological studies. However, of particular interest is the fact that some infected pigs develop a manifestation of scabies closely resembling human crusted scabies even in the absence of corticosteroid immunosuppression (11). Therefore, the porcine model provides a unique opportunity to study immunologic responses following scabies infection and may help to understand differences in individual susceptibility and why crusted scabies develops after scabies mite infestation.…”