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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02498

Peptides derived of kunitz-type serine protease inhibitor as potential vaccine against experimental schistosomiasis

Juan Hernández-Goenaga1, 2,  Julio Lopez-Aban1, 2*,  Anna V. Protasio3, 4, Belén Vicente1, 2,  Esther del Olmo1, Magnolia Vanevas5, Pedro Fernández-Soto1, 2,  Manuel A. Patarroyo5 and  Antonio Muro1, 2*
  • 1University of Salamanca, Spain
  • 2Institute of Biomedical Research of Salamanca (IBSAL), Spain
  • 3Wellcome Genome Campus, United Kingdom
  • 4Cambridge Institute for Medical Research, University of Cambridge, United Kingdom
  • 5Colombian Institute of Immunology Foundation, Colombia

Schistosomiasis is a significant public health problem in sub-Saharan Africa, China, South-East Asia and regions of South and central America affecting about 189 million people. Kunitz-type serine protease inhibitors have been identified as important players in the interaction of other flatworm parasites with their mammalian hosts. Here, we evaluate the protective efficacy of chemically synthesized of T- and B-cell peptide epitopes derived from a kunitz protein from Schistosoma mansoni. Putative kunitz-type protease inhibitor proteins were identified in the S. mansoni genome and their expression analyzed by RNA-seq. Gene expression analyses showed that the kunitz protein Smp_147730 (Syn. Smp_311670) was dramatically and significantly up-regulated in schistosomula and adult worms when compared to the invading cercariae. T- and B-cell epitopes were predicted using bioinformatics tools, chemically synthesized and formulated in the Adjuvant Adaptation (ADAD) vaccination system. BALB/c mice were vaccinated and challenged with S. mansoni cercariae. Kunitz peptides were highly protective in vaccinated BALB/c mice showing significant reductions in recovery of adult females (89-91%), and in the numbers of eggs trapped in the livers (77-81%) and guts (57-77%) of mice. Moreover, liver lesions were significantly reduced in vaccinated mice (64-65%) compared to infected control mice. The vaccination regime was well tolerated with both peptides. We propose the use of these peptides, alone or in combination, as reliable candidates for vaccination against schistosomiasis.

Keywords: Schistosoma mansoni, Helminth vaccines, synthetic peptide, ADAD vaccination system, Kunitz-type protein, immunomodulator AA0029

Received: 03 May 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Hernández-Goenaga, Lopez-Aban, Protasio, Vicente, del Olmo, Vanevas, Fernández-Soto, Patarroyo and Muro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Julio Lopez-Aban, University of Salamanca, Salamanca, 37008, Spain, jlaban@usal.es
Prof. Antonio Muro, University of Salamanca, Salamanca, 37008, Spain, ama@usal.es