title: Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.
abstract: Schistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now ready to move to clinical trials. In order to better assess Sm-p80 vaccine immunogenicity; here we used a systems biology approach employing RNA-sequencing to identify gene signatures and epistatic interactions following Sm-p80 vaccination in mouse and baboon models that may predict vaccine efficacy. Recombinant Sm-p80 + CpG-oligodeoxynucleotide (ODN) vaccine formulation induced both cellular and humoral immunity genes with a predominant TH1 response as well as TH2 and TH17 gene signatures. Early gene responses and gene-network interactions in mice immunized with rSm-p80 + ODN appear to be initiated through TLR4 signaling. CSF genes, S100A alarmin genes and TNFRSF genes appear to be a signature of vaccine immunogenicity/efficacy as identified by their participation in gene network interactions in both mice and baboons. These gene families may provide a basis for predicting desirable outcomes for vaccines against schistosomiasis leading to a better understanding of the immune system response to vaccination.
authors.affiliation: Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Lubbock, Texas, United States of America.
authors.forename: Juan U
authors.initials: JU
authors.lastname: Rojo
authors.affiliation: Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Amarillo, Texas, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Melkus
authors.affiliation: Center for Biotechnology and Genomics. Texas Tech University, Lubbock, Texas, United States of America.
authors.forename: Kameswara Rao
authors.initials: KR
authors.lastname: Kottapalli
authors.affiliation: Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Lubbock, Texas, United States of America.
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Okiya
authors.affiliation: Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Lubbock, Texas, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Sudduth
authors.affiliation: Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Lubbock, Texas, United States of America.|Department of Internal Medicine. Texas Tech University School of Medicine, Lubbock Texas, United States of America.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Lubbock, Texas, United States of America.|Department of Internal Medicine. Texas Tech University School of Medicine, Lubbock Texas, United States of America.
authors.forename: Adebayo J
authors.initials: AJ
authors.lastname: Molehin
authors.affiliation: PAI Life Sciences, Seattle, Washington, United States of America.|Infectious Disease Research Institute, Seattle, Washington, United States of America.|Department of Global Health, University of Washington, Seattle, Washington, United States of America.
authors.forename: Darrick
authors.initials: D
authors.lastname: Carter
authors.affiliation: Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Lubbock, Texas, United States of America.|Department of Internal Medicine. Texas Tech University School of Medicine, Lubbock Texas, United States of America.
authors.forename: Afzal A
authors.initials: AA
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D004843:Epistasis, Genetic / Q000235:genetics / Q000276:immunology; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010215:Papio; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D009838:Oligodeoxyribonucleotides; D014612:Vaccines