Identification of protective peptides of Fasciola hepatica-derived cathepsin L1 (FhCL1) in vaccinated sheep by a linear B-cell epitope mapping approach.
Animals
Antibodies, Helminth
/ immunology
Antigens, Helminth
/ immunology
Cathepsin L
Cathepsins
/ immunology
Cattle
Cattle Diseases
/ immunology
Enzyme-Linked Immunosorbent Assay
/ veterinary
Epitope Mapping
/ methods
Epitopes, B-Lymphocyte
/ immunology
Fasciola hepatica
/ immunology
Fascioliasis
/ immunology
Livestock
/ immunology
Models, Molecular
Molecular Conformation
Peptides
/ immunology
Sheep
Sheep Diseases
/ immunology
Vaccines
/ immunology
Cathepsin L1
Epitope mapping
Fasciola hepatica
Sheep
Vaccine
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
31 Jul 2020
31 Jul 2020
Historique:
received:
08
05
2020
accepted:
23
07
2020
entrez:
2
8
2020
pubmed:
2
8
2020
medline:
10
4
2021
Statut:
epublish
Résumé
Fasciolosis is one of the most important parasitic diseases of livestock. The need for better control strategies gave rise to the identification of various vaccine candidates. The recombinant form of a member of the cysteine protease family, cathepsin L1 of Fasciola hepatica (FhCL1) has been a vaccine target for the past few decades since it has been shown to behave as an immunodominant antigen. However, when FhCL1 was used as vaccine, it has been observed to elicit significant protection in some trials, whereas no protection was provided in others. In order to improve vaccine development strategy, we conducted a linear B-cell epitope mapping of FhCL1 in sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus Montanide and with significant reduction of the fluke burden, sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus aluminium hydroxide and with non-significant reduction of the fluke burden, and in unvaccinated-infected sheep. Our study showed that the pattern and dynamic of peptide recognition varied noticeably between both vaccinated groups, and that the regions 55-63 and 77-84, which are within the propeptide, and regions 102-114 and 265-273 of FhCL1 were specifically recognised only by vaccinated sheep with significant reduction of the fluke burden. In addition, these animals also showed significant production of specific IgG2, whereas none was observed in vaccinated-Aluminium hydroxide and in infected control animals. We have identified 42 residues of FhCL1 that contributed to protective immunity against infection with F. hepatica in sheep. Our results provide indications in relation to key aspects of the immune response. Given the variable outcomes of vaccination trials conducted in ruminants to date, this study adds new insights to improve strategies of vaccine development.
Sections du résumé
BACKGROUND
BACKGROUND
Fasciolosis is one of the most important parasitic diseases of livestock. The need for better control strategies gave rise to the identification of various vaccine candidates. The recombinant form of a member of the cysteine protease family, cathepsin L1 of Fasciola hepatica (FhCL1) has been a vaccine target for the past few decades since it has been shown to behave as an immunodominant antigen. However, when FhCL1 was used as vaccine, it has been observed to elicit significant protection in some trials, whereas no protection was provided in others.
METHODS
METHODS
In order to improve vaccine development strategy, we conducted a linear B-cell epitope mapping of FhCL1 in sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus Montanide and with significant reduction of the fluke burden, sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus aluminium hydroxide and with non-significant reduction of the fluke burden, and in unvaccinated-infected sheep.
RESULTS
RESULTS
Our study showed that the pattern and dynamic of peptide recognition varied noticeably between both vaccinated groups, and that the regions 55-63 and 77-84, which are within the propeptide, and regions 102-114 and 265-273 of FhCL1 were specifically recognised only by vaccinated sheep with significant reduction of the fluke burden. In addition, these animals also showed significant production of specific IgG2, whereas none was observed in vaccinated-Aluminium hydroxide and in infected control animals.
CONCLUSIONS
CONCLUSIONS
We have identified 42 residues of FhCL1 that contributed to protective immunity against infection with F. hepatica in sheep. Our results provide indications in relation to key aspects of the immune response. Given the variable outcomes of vaccination trials conducted in ruminants to date, this study adds new insights to improve strategies of vaccine development.
Identifiants
pubmed: 32736582
doi: 10.1186/s13071-020-04260-6
pii: 10.1186/s13071-020-04260-6
pmc: PMC7393625
doi:
Substances chimiques
Antibodies, Helminth
0
Antigens, Helminth
0
Epitopes, B-Lymphocyte
0
Peptides
0
Vaccines
0
Cathepsins
EC 3.4.-
cathepsin L1, Fasciola hepatica
EC 3.4.22.-
Cathepsin L
EC 3.4.22.15
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
390Subventions
Organisme : Horizon 2020 Framework Programme
ID : H2020-635408-PARAGONE
Organisme : Ministerio de Ciencia e Innovación (ES)
ID : AGL2015-67023-C2-1-R
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