Evaluation of immunogenicity and efficacy of Fasciola hepatica Tetraspanin 2 (TSP2) fused to E. coli Heat-Labile Enterotoxin B Subunit LTB adjuvant following intranasal vaccination of cattle

Zerna, Gemma, Rathinasamy, Vignesh A., Toet, Hayley, Anderson, Glenn, Dempster, Robert, Spithill, Terry W., and Beddoe, Travis (2021) Evaluation of immunogenicity and efficacy of Fasciola hepatica Tetraspanin 2 (TSP2) fused to E. coli Heat-Labile Enterotoxin B Subunit LTB adjuvant following intranasal vaccination of cattle. Vaccines, 9 (11). 1213.

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Abstract

Fasciolosis, caused by the liver flukes Fasciola hepatica and F. gigantica, 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 F. hepatica 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 Escherichia coli 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 F. hepatica 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.

Item ID: 75226
Item Type: Article (Research - C1)
ISSN: 2076-393X
Keywords: AB, toxin 5, Cattle, Fasciola hepatica, LTB, Mucosal immunity, Tegument membrane, Tetraspanin, Vaccine
Copyright Information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).
Funders: Australian Research Council (ARC)
Projects and Grants: ARC LP130100943, ARC LP160100442
Research Data: https://doi.org/10.26181/61074c202685b
Date Deposited: 11 Jul 2022 04:49
FoR Codes: 30 AGRICULTURAL, VETERINARY AND FOOD SCIENCES > 3009 Veterinary sciences > 300909 Veterinary parasitology @ 60%
30 AGRICULTURAL, VETERINARY AND FOOD SCIENCES > 3003 Animal production > 300304 Animal protection (incl. pests and pathogens) @ 40%
SEO Codes: 10 ANIMAL PRODUCTION AND ANIMAL PRIMARY PRODUCTS > 1001 Environmentally sustainable animal production > 100199 Environmentally sustainable animal production not elsewhere classified @ 40%
10 ANIMAL PRODUCTION AND ANIMAL PRIMARY PRODUCTS > 1004 Livestock raising > 100401 Beef cattle @ 30%
10 ANIMAL PRODUCTION AND ANIMAL PRIMARY PRODUCTS > 1004 Livestock raising > 100402 Dairy cattle @ 30%
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