Surprisingly, these abundant antibodies recognize their targets only when the proteins retain their native conformations, stabilized by the presence of intramolecular disulfide bridges

Surprisingly, these abundant antibodies recognize their targets only when the proteins retain their native conformations, stabilized by the presence of intramolecular disulfide bridges. mice, rats and Parathyroid Hormone (1-34), bovine humans on total extracts of larval or adult schistosomes revealed that a small number of antigen bands predominate in all cases. Recognition of each of these major bands was lost when the blots were run under reducing condition. We expressed a rationally selected group of schistosome tegumental membrane antigens in insect host cells, and used the membrane extracts of these cells to unambiguously identify the major antigens recognized by infected mouse, rat and human serum. These results revealed that a limited number of dominant, reduction-sensitive conformational epitopes on five major tegumental surface membrane proteins: SmTsp2, Sm23, Sm29, SmLy6B and SmLy6F, are primary targets of mouse, rat and human infection sera antibodies. We conclude that, infection of both permissive (mouse) and non-permissive (rat) rodent models, as well as humans, elicit a dominant antibody response recognizing a limited number of conformational epitopes on the same five tegumental membrane proteins. Thus it appears that neither infecting schistosomula nor mature adult schistosomes are substantively impacted by the robust circulating anti-tegumental antibody response they elicit to these Parathyroid Hormone (1-34), bovine antigens. Importantly, our data suggest a need to re-evaluate host immune responses to many schistosome antigens and has important implications regarding schistosome immune evasion mechanisms and schistosomiasis vaccine development. Author Summary Schistosomiasis is caused by blood flukes residing in the veins of infected individuals and afflicts millions of people in the developing world. The schistosome worms can remain healthy in the bloodstream for more than 10 years, implying an extraordinary ability to evade host immune damage. Scientists are seeking to understand immune evasion so as to find weaknesses in defenses that can be exploited in the development of effective vaccines. Here we investigate the normal antibody response to schistosomes during infection of mice, rats and humans, and show for the first time that this response is highly skewed to the recognition of a small number of proteins present at the worm surface. Surprisingly, these abundant antibodies recognize their targets only when the proteins retain their native conformations, stabilized by the presence of intramolecular disulfide bridges. Because of this conformational-dependence, these antibodies have remained undetected in prior studies in which antibody binding Parathyroid Hormone (1-34), bovine assays were routinely performed in a reducing environment that destroys disulfide bridges. The routine presence of these antibodies within the serum of schistosome infected patients and animals raises new and interesting questions as to their possible role in immune evasion, and has significant implications for schistosomiasis vaccine development. Introduction Schistosomiasis is a disease Parathyroid Hormone (1-34), bovine affecting more than 200 million individuals living mostly Parathyroid Hormone (1-34), bovine in underdeveloped tropical and subtropical regions (http://www.who.int/mediacentre/factsheets/fs115/en/). The disease is caused by infection with FOXO3 schistosome blood flukes which can survive, if untreated, for decades inside the vascular system of immune competent permissive hosts. Illness is primarily a consequence of immunopathology from schistosome eggs trapped in tissues (reviewed by [1]). Despite the long term presence of adult worms in their vascular system, permissive hosts, by definition, do not typically develop immune responses directed at juvenile or adult worms [2] that are capable of preventing new infections or eliminating all adult worms. This is not to imply that anti-worm immune responses are completely ineffective, as a measure of protective immunity following multiple rounds of reinfection has been documented [3, 4]. The humoral response to schistosome infection has been extensively characterized in efforts to identify antigens for use in the diagnosis of infection or that might.