Evaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle

Fasciolosis, caused by the liver flukes <i>Fasciola hepatica</i> and <i>F. gigantica,</i> is an economically important and globally distributed zoonotic disease. Liver fluke infections in livestock cause significant losses in production and are of particular concern to region...

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Autores principales: Gemma Zerna, Vignesh A. Rathinasamy, Hayley Toet, Glenn Anderson, Robert Dempster, Terry W. Spithill, Travis Beddoe
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:4069320d163d48e481e81c2abb2742e22021-11-25T19:10:04ZEvaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle10.3390/vaccines91112132076-393Xhttps://doaj.org/article/4069320d163d48e481e81c2abb2742e22021-10-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1213https://doaj.org/toc/2076-393XFasciolosis, caused by the liver flukes <i>Fasciola hepatica</i> and <i>F. gigantica,</i> is an economically important and globally distributed zoonotic disease. Liver fluke infections in livestock cause significant losses in production and are of particular concern to regions where drug resistance is emerging. Antigens of the <i>F. hepatica</i> surface tegument represent promising vaccine candidates for controlling this disease. Tetraspanins are integral tegumental antigens that have shown partial protection as vaccine candidates against other trematode species. The <i>Escherichia coli</i> heat-labile enterotoxin’s B subunit (LTB) is a potent mucosal adjuvant capable of inducing an immune response to fused antigens. This study investigates the potential of <i>F. hepatica</i> tetraspanin 2 extracellular loop 2 (rFhTSP2) as a protective vaccine antigen and determines if fusion of FhTSP2 to LTB can enhance protection in cattle. Cattle were immunised subcutaneously with rFhTSP2 mixed in the Freund’s adjuvant and intranasally with rLTB-FhTSP2 in saline, accounting for equal molar ratios of tetraspanin in both groups. Vaccination with rFhTSP2 stimulated a strong specific serum IgG response, whereas there was no significant serum IgG response following rLTB-FhTSP2 intranasal vaccination. There was no substantial antigen specific serum IgA generated in all groups across the trial. Contrastingly, after the fluke challenge, a rise in antigen specific saliva IgA was observed in both vaccination groups on Day 42, with the rLTB-FhTSP2 vaccination group showing significant mucosal IgA production at Day 84. However, neither vaccine group showed a significant reduction of fluke burden nor faecal egg output. These results suggest that intranasal vaccination with rLTB-FhTSP2 does elicit a humoral mucosal response but further work is needed to evaluate if mucosal delivery of liver fluke antigens fused to LTB is a viable vaccine strategy.Gemma ZernaVignesh A. RathinasamyHayley ToetGlenn AndersonRobert DempsterTerry W. SpithillTravis BeddoeMDPI AGarticlevaccine<i>Fasciola hepatica</i>LTBAB<sub>5</sub> toxintetraspanintegument membraneMedicineRENVaccines, Vol 9, Iss 1213, p 1213 (2021)
institution DOAJ
collection DOAJ
language EN
topic vaccine
<i>Fasciola hepatica</i>
LTB
AB<sub>5</sub> toxin
tetraspanin
tegument membrane
Medicine
R
spellingShingle vaccine
<i>Fasciola hepatica</i>
LTB
AB<sub>5</sub> toxin
tetraspanin
tegument membrane
Medicine
R
Gemma Zerna
Vignesh A. Rathinasamy
Hayley Toet
Glenn Anderson
Robert Dempster
Terry W. Spithill
Travis Beddoe
Evaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle
description Fasciolosis, caused by the liver flukes <i>Fasciola hepatica</i> and <i>F. gigantica,</i> is an economically important and globally distributed zoonotic disease. Liver fluke infections in livestock cause significant losses in production and are of particular concern to regions where drug resistance is emerging. Antigens of the <i>F. hepatica</i> surface tegument represent promising vaccine candidates for controlling this disease. Tetraspanins are integral tegumental antigens that have shown partial protection as vaccine candidates against other trematode species. The <i>Escherichia coli</i> heat-labile enterotoxin’s B subunit (LTB) is a potent mucosal adjuvant capable of inducing an immune response to fused antigens. This study investigates the potential of <i>F. hepatica</i> tetraspanin 2 extracellular loop 2 (rFhTSP2) as a protective vaccine antigen and determines if fusion of FhTSP2 to LTB can enhance protection in cattle. Cattle were immunised subcutaneously with rFhTSP2 mixed in the Freund’s adjuvant and intranasally with rLTB-FhTSP2 in saline, accounting for equal molar ratios of tetraspanin in both groups. Vaccination with rFhTSP2 stimulated a strong specific serum IgG response, whereas there was no significant serum IgG response following rLTB-FhTSP2 intranasal vaccination. There was no substantial antigen specific serum IgA generated in all groups across the trial. Contrastingly, after the fluke challenge, a rise in antigen specific saliva IgA was observed in both vaccination groups on Day 42, with the rLTB-FhTSP2 vaccination group showing significant mucosal IgA production at Day 84. However, neither vaccine group showed a significant reduction of fluke burden nor faecal egg output. These results suggest that intranasal vaccination with rLTB-FhTSP2 does elicit a humoral mucosal response but further work is needed to evaluate if mucosal delivery of liver fluke antigens fused to LTB is a viable vaccine strategy.
format article
author Gemma Zerna
Vignesh A. Rathinasamy
Hayley Toet
Glenn Anderson
Robert Dempster
Terry W. Spithill
Travis Beddoe
author_facet Gemma Zerna
Vignesh A. Rathinasamy
Hayley Toet
Glenn Anderson
Robert Dempster
Terry W. Spithill
Travis Beddoe
author_sort Gemma Zerna
title Evaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle
title_short Evaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle
title_full Evaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle
title_fullStr Evaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle
title_full_unstemmed Evaluation of Immunogenicity and Efficacy of <i>Fasciola hepatica</i> Tetraspanin 2 (TSP2) Fused to <i>E. coli</i> Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle
title_sort evaluation of immunogenicity and efficacy of <i>fasciola hepatica</i> tetraspanin 2 (tsp2) fused to <i>e. coli</i> heat-labile enterotoxin b subunit ltb adjuvant following intranasal vaccination of cattle
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/4069320d163d48e481e81c2abb2742e2
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