Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm

PLoS Pathogens
Neima BriggsPeter J Hotez

Abstract

Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD). Current control measures focused on mass deworming have had limited success due to low drug efficacies. Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission. Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model. The recombinant WAP protein (rTm-WAP49), as well as a single, highly conserved repeat within WAP (fragment 8) expressed as an Na-GST-1 fusion protein (rTm-WAP-F8+Na-GST-1), generate a strong T helper type 2 (Th2) immune response when delivered as subcutaneous vaccines formulated with Montanide ISA 720. Oral challenge with T. muris infective eggs following vaccination led to a significant reduction in worm burden of 48% by rTm-WAP49 and 33% by rTm-WAP-F8+Na-GST-1. The cellular immune correlates of protection included significant antigen-specific production of Th2 cytokines IL-4, IL-9, and IL-13 by cells isolated from the v...Continue Reading

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Datasets Mentioned

BETA
KHJ42268.1

Methods Mentioned

BETA
cDNA library
ELISA
ISA
light microscopy
enzyme-linked immunosorbent assay
PMA

Software Mentioned

GraphPad
BLAST
Tidyverse
coin
Plex Manager
TreeDyn
readxl
CLUSTAL W
Hmisc
SignalP

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