Abstract
Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
Highlights
Schistosomiasis is a chronic, often debilitating, parasitic disease affecting over 200 million people worldwide and killing at least 300,000 people annually [1]
We take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas to pilot an immunomics approach to the discovery of vaccine antigens
Antibody profiles correlate with infection intensity Given the distinct roles of different immunoglobulin isotypes and IgG subclasses in chronic helminth infections, and to gain a comprehensive picture of antibody reactivity from putatively resistant (PR) versus chronically infected (CI) individuals, we analyzed IgG1, IgG3, IgG4 and IgE responses to soluble worm antigen preparation (SWAP) and a panel of schistosome antigens
Summary
Schistosomiasis is a chronic, often debilitating, parasitic disease affecting over 200 million people worldwide and killing at least 300,000 people annually [1]. Adult flukes live in the portal and mesenteric veins (Schistosoma mansoni and S. japonicum) or in the veins of the bladder (S. haematobium), as male/female pairs, and survive for many years producing hundreds of fertilized eggs per day. Severe morbidity results from the host immune responses to eggs that become trapped in the tissues, including periportal fibrosis, portal hypertension, urinary obstruction and bladder carcinoma [4]. Chemotherapy with praziquantel (PZQ) is the standard treatment for schistosomiasis. Despite recent large-scale MDA efforts [8], integrated control programs aimed at limiting schistosomiasis by improving education and sanitation, molluscicide treatment programs to reduce the population of the intermediate snail host, and chemotherapy have had limited success [5,9].
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