An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas

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.

Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

“…Using an immunomic approach (48–50), we profiled host antibody responses to a subset of parasite stage-specific proteins (397 proteins). These selected proteins (https://exon.niaid.nih.gov/transcriptome/O_volvulus/Additional_file_14.xlsx) were printed on a protein array, quality checked, and assessed for isotype-specific antibody responses (IgG1, IgG3, IgG4, and IgE) (Fig.…”

Immunomics: a 21st century approach to vaccine development for complex pathogens

“…These include the tetraspanin SmTSP-2, the tegumental antigen Sm29, and the very low-density lipoprotein-binding protein SjSVLBP as well as other novel proteins (reviewed in (McWilliam et al 2012). More recently, these protein microarrays have been screened for IgE and multiple IgG subclasses responses using sera from resistant or susceptible individuals (Gaze et al 2014). The resultant antibody profiles could distinguish between protected vs non-protected cohorts and allowed identification of antigens that might represent excellent vaccine candidates (Gaze et al 2014).…”

Development of a schistosomiasis vaccine

“…Human correlate studies revealed Sm-p80-reactivity with IgG in human sera from individuals that are naturally resistant to schistosome infection [48]. Equally important is the absence of prevailing Sm-p80-specific IgE in a high risk/infected populations, thus minimizing the risk of hypersensitivity reaction following vaccination with Sm-p80 in humans [48;54]. It is noteworthy that the Sm-p80 vaccine has also been demonstrated to offer cross-species protection against S. haematobium infections in hamsters and baboons [55] as well as against S. japonicum infections in mice [25;56].…”