Abstract
Schistosomiasis is a major disease of the developing world for which no vaccine has been successfully commercialized. While numerous Schistosoma mansoni worm antigens have been identified that elicit antibody responses during natural infections, little is known as to the identities of the schistosome antigens that are most prominently recognized by antibodies generated through natural infection. Non-reducing western blots probed with serum from schistosome-infected mice, rats and 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 S. mansoni 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 S. mansoni infection sera antibodies. We conclude that, Schistosoma mansoni 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 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.
Highlights
Schistosomiasis is a disease affecting more than 200 million individuals living mostly in underdeveloped tropical and subtropical regions
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
Western blots of total larval and adult S. mansoni extracts probed by sera from recently infected mice, rats or humans
Summary
Schistosomiasis is a disease affecting more than 200 million individuals living mostly in underdeveloped tropical and subtropical regions (http://www.who.int/mediacentre/factsheets/fs115/ en/). 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. Examples include comparisons in schistosome antigen recognition by: 1) non-permissive rats vs permissive mice models [5, 6]; 2) mice +/- vaccination by irradiated cercariae [7], and; 3) humans displaying susceptibility vs putative resistance to infection [8, 9] Through these efforts, dozens of schistosome antigens have been found to be recognized by antibodies in serum from infected humans or rodents (reviewed by [10,11,12]). This information could aid in understanding the nature of the normal humoral immune response to schistosome infection and provide important guidance to efforts seeking improved diagnostic tools and new vaccines
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