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

PLoS Pathogens

Jeroen Pollet¹  Leroy Versteeg²  Junfei Wei³  Bin Zhan⁴  Neima Briggs⁵  Ashish Damania⁶  Kelly S. Hayes⁷  Brian Keegan⁸ 

[1]Department of Biology, Baylor University, Waco, Texas, United States of America

[2]Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America

[3]MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, Texas, United States of America

[4]School of Biological Sciences, FBMH, MAHSC, University of Manchester, Manchester, United Kingdom

[5]Texas Childrens Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, United States of America

[6]The Lydia Becker Institute for Immunology and Inflammation, University of Manchester, Manchester, United Kingdom

[7]Uniformed Services University of the Health Sciences, UNITED STATES

[8]Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom

DOI  :  10.1371/journal.ppat.1007273

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 vaccine-draining inguinal lymph nodes, parasite-draining mesenteric lymph nodes, and spleen in mice vaccinated with either rTm-WAP49 or rTm-WAP-F8+Na-GST-1. The humoral immune correlates included a high antigen-specific ratio of IgG1 to IgG2a, without eliciting an IgE-mediated allergic response. Immunofluorescent staining of adult T. muris with WAP antisera identified the worm’s pathogenic stichosome organ as the site of secretion of native Tm-WAP protein into the colonic mucosa. Given the high sequence conservation for the WAP proteins from T. muris and T. trichiura, the results presented here support the WAP protein to be further evaluated as a potential human whipworm vaccine candidate.

【 授权许可】

CC BY