Distinct antigen recognition pattern during zoonotic visceral leishmaniasis in humans and dogs

Abstract

Leishmania infantum is a causative agent of endemic zoonotic visceral leishmaniasis (VL) in regions of South America and the Mediterranean. Dogs are the major reservoirs for Leishmania infantum in these regions, and control of disease in dogs could have a significant impact on human disease. Although dogs share many symptoms of VL with humans as a result of L. infantum infection, they also show some unique clinical manifestations, which are often a combination of visceral and cutaneous leishmaniasis, suggesting different mechanisms of disease development in dogs and humans. Here, we compare antibody responses of dogs and humans with VL to various defined leishmanial antigens. Parasite lysate and K39, the two most commonly used antigens for serodiagnosis of VL, detected the highest levels of antibodies in both humans and dogs with VL, whereas the recognition patterns of these antigens were distinct between the hosts. Among other defined antigens tested, LmSTI1 and CPB detected higher levels of antibodies in dogs and humans, respectively. These results indicate there is a difference between humans and dogs in antigen recognition patterns during VL; we infer that different strategies may need to be used in development of vaccines and diagnostics for humans and for dogs. In addition, we show a correlation between antibody titers to several antigens and severity of clinical symptoms during canine VL.

Characterization of Novel Leishmania infantum Recombinant Proteins Encoded by Genes from Five Families with Distinct Capacities for Serodiagnosis of Canine and Human Visceral Leishmaniasis

“…As detailed above, the recombinant proteins evaluated in this work displayed different capacities to react with antibodies from dogs naturally infected with L. infantum and from humans with VL. The present work and data reported by other investigators 62 suggest that repertoires of humoral immune responses in dogs and humans infected with L. infantum are different, and that this difference should be taken into account when developing serodiagnostic methods. Because no antigen, even if it has a high sensitivity and specificity in ELISAs for detection of antibodies against L. infantum , was able to detect all dogs or humans that acquired the infection and produced specific antibodies, immunodiagnostic assays should be developed on a platform appropriate to show reactivity to several recombinant antigens simultaneously ( http:// www.chembio.com/newtechnologies.html ).…”

Application of an Improved Enzyme-Linked Immunosorbent Assay Method for Serological Diagnosis of Canine Leishmaniasis

“…The recombinant protein rK39, which is a repetitive immunodominant epitope of a kinesin-related protein expressed predominantly in the amastigotes of viscerotropic L. chagasi (syn. L. infantum) (6), has proved to be an exceptionally strong marker of disease (16). Nevertheless, rK39 performs suboptimally in asymptomatic cases with proven infection (22).…”

Evaluation of Ex Vivo Human Immune Response against Candidate Antigens for a Visceral Leishmaniasis Vaccine

“…prepared from L. donovani promastigotes by sonication, as previously described. 13 Endotoxin content of all the proteins used in WBA was less than 100 EU/mg. Phytohaemagglutinin (PHA) and phosphate-buffered saline (PBS) were used as positive and negative controls, respectively.…”

“…Recombinant proteins of the other genes were produced in previous studies. 8,13,14 Soluble Leishmania antigen (SLA) was…”