In silico prediction of binding of promiscuous peptides to multiple MHC class-II molecules identifies the Th1 cell epitopes from secreted and transmembrane proteins of Schistosoma japonicum in BALB/c mice.

It has not so far been possible to identify rapidly and effectively the anti-schistosomiasis Th cell epitopes that are capable of simulating IFN-γ (Interferon-gamma)-mediated Th1-type protective immunity in response to radiation-attenuated schistosome cercaria. With the advance of the omics studies of schistosomes, an approach that used reverse vaccinology probably resolved the above problems. In this "proof-of-principle" study, first, we selected 31 secreted or transmembrane protein sequences sampled from sequences of the transcriptome of Schistosoma japonicum, and analyzed characteristics of these proteins by using conventional bioinformatics tools. Second, putative promiscuous Th cell epitopes within these proteins were predicted using three to four different immuno-informatics algorithms for the prediction of MHC (Major Histocompatibility Complex) class-II binding peptides. We predicted using these in silico approaches promiscuous Th cell epitopes that are capable of binding to both murine and human MHC class-II molecules. To validate our in silico prediction experimentally, BALB/c mice were immunized with the five predicted peptides, and the proliferative responses and cytokine production of lymphocytes from the immunized BALB/c mice were assessed in vitro by modified MTT (Methyl Thiazolyl Tetrazolium), ELISA (Enzyme-linked Immunosorbent Assay) and flow cytometry methods. The results showed that two of the five predicted peptides could induce a Th1-type response in vitro. These results suggest that promiscuous Th1 cell epitopes from secreted or transmembrane proteins of S. japonicum can be identified using a strategy of reverse vaccinology.

[Application of reverse vaccinology in Schistosoma vaccine development: advances and prospects].

OBJECTIVE: Current advances in reverse vaccinology based on the principle of "sequence-structure-function" and such integrated platform technologies as immunoinformatics, computer-aid design, and various high-throughput omics (including genomics, transcriptomics and proteomics) may pave a new way for the discovery of candidate vaccine molecules against schistosomiasis. Both theoretical prediction and experimental approaches conventionally used in the field of reverse vaccinology are briefly introduced in this review; and the applications of these approaches to screening and confirming candidate Schistosoma vaccine molecules are also summarized. Furthermore, potential research prospects of the application of reverse vaccinology to Schistosoma vaccine development are discussed by simulating immune effect mechanisms of immunization with radiation-attenuated cercaria vaccine in animal hosts and naturally acquired immunity in human population.