Promising Plant-Derived Adjuvants in the Development of Coccidial Vaccines

Abstract

Coccidial parasites cause medical and veterinary diseases worldwide, frequently leading to severe illness and important economic losses. At present, drugs, chemotherapeutics and prophylactic vaccines are still missing for most of the coccidial infections. Moreover, the development and administration of drugs and chemotherapeutics against these diseases would not be adequate in livestock, since they may generate unacceptable residues in milk and meat that would avoid their commercialization. In this scenario, prophylactic vaccines emerge as the most suitable approach. Subunit vaccines have proven to be biologically safe and economically viable, allowing researchers to choose among the best antigens against each pathogen. However, they are generally poorly immunogenic and require the addition of adjuvant compounds to the vaccine formulation. During the last decades, research involving plant immunomodulatory compounds has become an important field of study based on their potential pharmaceutical applications. Some plant molecules such as saponins, polysaccharides, lectins and heat shock proteins are being explored as candidates for adjuvant/carriers formulations. Moreover, plant-derived immune stimulatory compounds open the possibility to attain the main goal in adjuvant research: a safe and non-toxic adjuvant capable of strongly boosting and directing immune responses that could be incorporated into different vaccine formulations, including mucosal vaccines. Here, we review the immunomodulatory properties of several plant molecules and discuss their application and future perspective as adjuvants in the development of vaccines against coccidial infections.

Keywords: coccidial parasites; heat shock proteins; lectins; plant-derived adjuvants; polysaccharides; saponins; vaccines.

Figure 1

Classification of adjuvants. Type A adjuvants interact with pattern recognition receptors (such as Toll like receptors) and act as immune-potentiators of the immune response (e.g., MPL). Type B adjuvants function as delivery systems by improving the recruitment of innate immune cells and favoring the Ag capture (e.g., Alum, MF59, CFA, IFA). Type C adjuvants are those compounds that act through co-stimulatory molecules (CD28) present in T cells (e.g., TGN1412).

Figure 2

Molecular structure of Rg2 saponin from traditional Chinese medicinal herbs with adjuvant activities.

Figure 3

Common structural moiety of many bioactive polysaccharides.

Figure 4

Homotetrameric assembly of Lectin UEA-II from Ulex europaeus (10.2210/pdb1dzq/pdb). This assembly was defined by Loris et al. (112). The crystal structure was determined using X-ray diffraction at a resolution of 2.85 Å and downloaded from the protein data bank: http://www.rcsb.org/.

Figure 5

Scheme of the domain structure of yeast Hsp90 (A) and E. coli Hsp70 (B), defined by limited proteolysis and structural studies. Hsp90s have an N-terminal peptide binding domain (N), a middle segment (M) that interacts with client proteins and contributes with ATP hydrolysis, and a C-terminal domain (C), involved in homodimerization. Hsp70s consist of an N-terminal ATPase domain (N) followed by a substrate binding domain (S) and a C-terminal domain (C), which forms a lid-like structure over the substrate-binding pocket that helps trap substrates in the substrate binding domain.