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

  • External authors:
  • Ayat Zawawi
  • Iris Mair
  • Murtala Jibril
  • Munirah Albaqshi

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In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection. / Zawawi, Ayat; Forman, Ruth; Smith, Hannah; Mair, Iris; Jibril, Murtala; Albaqshi, Munirah; Brass, Andrew; Derrick, Jeremy; Else, Kathryn.

In: PL o S Pathogens, Vol. 16, No. 3, e1008243, 23.03.2020.

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Zawawi, Ayat ; Forman, Ruth ; Smith, Hannah ; Mair, Iris ; Jibril, Murtala ; Albaqshi, Munirah ; Brass, Andrew ; Derrick, Jeremy ; Else, Kathryn. / In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection. In: PL o S Pathogens. 2020 ; Vol. 16, No. 3.

Bibtex

@article{80b9519d7c524a55b37d4e4f489ad356,
title = "In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection",
abstract = "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{\textquoteright}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. ",
author = "Ayat Zawawi and Ruth Forman and Hannah Smith and Iris Mair and Murtala Jibril and Munirah Albaqshi and Andrew Brass and Jeremy Derrick and Kathryn Else",
year = "2020",
month = mar,
day = "23",
doi = "10.1371/journal.ppat.1008243",
language = "English",
volume = "16",
journal = "PL o S Pathogens",
issn = "1553-7374",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection

AU - Zawawi, Ayat

AU - Forman, Ruth

AU - Smith, Hannah

AU - Mair, Iris

AU - Jibril, Murtala

AU - Albaqshi, Munirah

AU - Brass, Andrew

AU - Derrick, Jeremy

AU - Else, Kathryn

PY - 2020/3/23

Y1 - 2020/3/23

N2 - 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.

AB - 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.

U2 - 10.1371/journal.ppat.1008243

DO - 10.1371/journal.ppat.1008243

M3 - Article

VL - 16

JO - PL o S Pathogens

JF - PL o S Pathogens

SN - 1553-7374

IS - 3

M1 - e1008243

ER -