Journal Article

In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection

Smith, Hannah, Mair, Iris, Albaqshi, Munirah H., Derrick, Jeremy P., Brass, Andrew, Jibril, Murtala, Zawawi, Ayat, Else, Kathryn J., Forman, Ruth

2020

Overview

Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children's educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T-cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). Bone marrow-derived dendritic cells and bone marrow-derived macrophages responded in vitro to VLPs irrespective of whether the VLP also included T-cell epitopes. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T-cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Anopheles / Antibodies / Antibodies, Helminth - immunology / Antigen-presenting cells / Antigenic determinants / Antigens / Binding sites / Bioinformatics / Biology / Biology and Life Sciences / Bone marrow / CD4 antigen / Colitis / Computer Simulation / Core protein / Cytokines / Dendritic cells / Dendritic Cells - immunology / Dwarfism / Dysentery / Epitopes / Epitopes, T-Lymphocyte - administration & dosage / Epitopes, T-Lymphocyte - genetics / Epitopes, T-Lymphocyte - immunology / Epstein-Barr virus / Genomes / Genomics / Growth rate / Health aspects / Hepatitis / Hepatitis B / Hepatitis B core antigen / Histocompatibility Antigens Class II - genetics / Histocompatibility Antigens Class II - immunology / Humans / Hyperplasia / Immunogenicity, Vaccine / Immunoglobulin M / Immunology / Infections / Inflammation / Lymph nodes / Lymphocytes T / Lysosomes / Macrophages / Macrophages - immunology / Major histocompatibility complex / Male / Medicine / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Parasites / Poverty / Production management / Proteins / Roundworm infections / Supervision / Systematic review / T cells / Trichuriasis - immunology / Trichuriasis - parasitology / Trichuriasis - prevention & control / Trichuris - genetics / Trichuris - immunology / Vaccination / Vaccines / Vaccines - administration & dosage / Vaccines - genetics / Vaccines - immunology / Virus-like particles / Viruses / Waterborne diseases / Web sites (World Wide Web)