Abstract

Due to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.

Highlights

  • The protective immune response in sheep against Teladorsagia circumcincta infection has been studied extensively and is associated with lower worm egg productionMachín et al Vet Res (2021) 52:89Until recently, control of T. circumcincta has been focused on the use of chemotherapeutics, but nematode resistance against anthelmintics has made this approach unsustainable [6]

  • Measurement of antibody responses to parasite and vaccine antigens in serum In order to evaluate if the vaccine has induced some variations in the humoral immune response against this worm, the response to the Fourth stage larval (L4) stage -target of the protective immunity in sheep- was firstly analysed in vaccinated and non-vaccinated infected groups of both breeds

  • Naturally or experimentally-induced protection against T. circumcincta following infection is a complex phenomenon in which several immunoglobulins such as IgA, IgE, IgG, cells such as eosinophils, mast cells, globule leukocytes (GL), ­CD4+, plasmatic cells and other factors, like Interleukin 4 (IL-4) and/or 5 or galectins are implicated

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Summary

Introduction

Control of T. circumcincta has been focused on the use of chemotherapeutics, but nematode resistance against anthelmintics has made this approach unsustainable [6]. Due to this issue, it is important to find alternative control measures, such as vaccination; understanding the mechanisms underlying the protective immune response is essential for the development of a successful vaccine [7]. Previous successful prototype vaccines against GIN were only effective in their native forms, preventing global distribution and commercialisation This recombinant prototype has some features which could overcome this hurdle but, as with other prototype recombinant vaccines against GINs, repeated trials have shown variability in protective response [9]. The combination of 8 antigens in a single vaccine makes its production prohibitively expensive and simplifying the vaccine would be very desirable

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